Heteroarylpyranopyrazolyl derivatives for the treatment of inflammation

ABSTRACT

A class of benzopyranopyrazolyl derivatives is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula I ##STR1## wherein A is --(CH 2 ) m  --X--(CH 2 ) n  --; wherein X is S(O) p  or O; wherein m is 0 or 1; wherein n is 0 or 1; wherein p is 0 or 1; wherein B is selected from phenyl and five and six membered heteroaryl; wherein R 1  is selected from lower haloalkyl, cyano, formyl, lower alkoxycarbonyl, lower alkoxy, lower N-alkylaminocarbonyl, N-phenylaminocarbonyl, lower N,N-dialkylaminocarbonyl and lower N-alkyl-N-phenylaminocarbonyl; wherein R 2  is phenyl substituted at a substitutable position with a radical selected from lower alkylsulfonyl and sulfamyl; and wherein R 4  is one or more radicals selected from hydrido, halo, lower alkylthio, lower alkylsulfinyl, lower alkyl, cyano, carboxyl, lower alkoxycarbonyl, aminocarbonyl, lower haloalkyl, hydroxyl, lower alkoxy, amino, lower N-alkylamino, lower N,N-dialkylamino, lower hydroxyalkyl and lower haloalkoxy; or a pharmaceutically-acceptable salt thereof.

This is a divisional application of U.S. application 08/309,291, filedSep. 20, 1994.

FIELD OF THE INVENTION

This invention is in the field of antiinflammatory pharmaceutical agentsand specifically relates to compounds, compositions and methods fortreating inflammation and inflammation-associated disorders, such asarthritis.

BACKGROUND OF THE INVENTION

Prostaglandins play a major role in the inflammation process and theinhibition of prostaglandin production, especially production of PGG₂,PGH₂ and PGE₂, has been a common target of antiinflammatory drugdiscovery. However, common non-steroidal antiinflammatory drugs (NSAIDs)that are active in reducing the prostaglandin-induced pain and swellingassociated with the inflammation process are also active in affectingother prostaglandin-regulated processes not associated with theinflammation process. Thus, use of high doses of most common NSAIDs canproduce severe side effects, including life threatening ulcers, thatlimit their therapeutic potential. An alternative to NSAIDs is the useof corticosteroids, which have even more drastic side effects,especially when long term therapy is involved.

Previous NSAIDs have been found to prevent the production ofprostaglandins by inhibiting enzymes in the human arachidonicacid/prostaglandin pathway, including the enzyme cyclooxygenase (COX).The recent discovery of an inducible enzyme associated with inflammation(named "cyclooxygenase II (COX II)" or "prostaglandin G/H synthase II")provides a viable target of inhibition which more effectively reducesinflammation and produces fewer and less drastic side effects.

The novel compounds described herein are such safe and also effectiveantiinflammatory agents. The invention compounds are found to showusefulness in vivo as antiinflammatory agents with minimal side effects.The compounds described herein preferably selectively inhibitcyclooxygenase II over cyclooxygenase I.

Substituted pyrazoles having antiinflammatory activity are described incopending applications 08/160,594 and 08/160,553.

U.S. Pat. No. 3,940,418 to R. Hamilton describes tricyclic4,5-dihydrobenz[g]indazole-3-carboxylic acids as antiinflammatoryagents.

U.S. Pat. No. 4,803,193 to Kanda et al, describesspiro[3-alkyl-1-aryl[1]benzopyrano[4,3-c]pyrazole-4(1H),9'-[9H]fluorenesas heat sensitive recording matertials.

V. Colota et al (J.Med.Chem., 33, 2646 (1991)) describe tricyclicheteroaramatic systems, including 1-aryl-pyrazolo[4,5-c]quinolin-4-ones,1-aryl-pyrazolo[4,5-c][1,8]naphthyridin-4-ones and 1-aryl-[1]benzopyrano[3,4-d]pyrazol-4-ones for CNS aplications. F. Melani et al [J.Med.Chem.,29, 291 (1986) also describe 1-phenyl-pyrazolo [4,5-c]quinolines for CNSapplications.

U.S. Pat. Nos. 4,816,467 and 5,206,258 to Doria et al describe(2-cyano-3-(1,4-dihydro)-1-phenyl-[1]benzothiopyrano[4,3-c]pyrazol-3-yl)-3-oxo-propanamides as immunomodulators. G. Doria etal (Farmaco, 46, 843 (1991)) also describe the immunomodulating activityof pyrazolylpropanamides, and specifically ethyl[1-(4-fluorophenyl)-1,4-dihydro-[1]benzothiopyrano[4,3-c]pyrazole]-3-carboxylate.British patent 2,227,741 describes related benzopyrano[4,3-c]pyrazolesand benzothiopyrano[4,3-c]pyrazoles. European application No. 347,773similarly describes such fused pyrazole compounds, and specificallyα-cyano-N,1-bis(4-fluorophenyl)-β-oxo-1H-[1]benzothieno[3,2-c]pyrazole-3-propanamide.U.S. Pat. No. 5,260,328 to Doria et al describes2-cyano-3-(1,4-dihydro)-1-phenyl-[1]benzothiopyrano[4,3-c]pyrazol-3-yl)-3-oxo-propanamidesfor the treatment of rheumatoid arthritis.

U.S. Pat. No. 4,678,499 to Pasteris et al describes1-aryl-indenopyrazol-4-one-5-sulfonamides as having herbicidal activity.Specifically, 1-phenylindenopyrazol-4-one-5-sulfonamide and1,4-dihydro-N-[[(4-methoxy-6-methyl-2-pyrimidinyl)amino]carbonyl]-3-methyl-1-[4-(methylsulfonyl)phenyl]-4-oxo-indeno[1,2-c]pyrazole-5-sulfonamideare described.

However, the benzopyranopyrazolyl derivatives of the present inventionhave not been previously described.

DESCRIPTION OF THE INVENTION

A class of compounds useful in treating inflammation-related disordersis defined by Formula I: ##STR2##

wherein A is --(CH₂)_(m) --X--(CH₂)_(n) --;

wherein X is selected from S(O)_(p), O and NR³ ;

wherein m is 0 to 3, inclusive;

wherein n is 0 to 3, inclusive;

wherein p is 0 to 2, inclusive;

wherein B is selected from aryl and heteroaryl;

wherein R¹ is selected from hydrido, halo, haloalkyl, cyano, nitro,formyl, alkoxycarbonyl, carboxyl, carboxyalkyl, alkoxycarbonylalkyl,amidino, cyanoamidino, aminocarbonyl, alkoxy, alkoxyalkyl,aminocarbonylalkyl, N-alkylaminocarbonyl, N-arylaminocarbonyl,N,N-dialkylaminocarbonyl, N-alkyl-N-arylaminocarbonyl, alkylcarbonyl,alkylcarbonylalkyl, hydroxyalkyl, alkylthio, alkylsulfinyl,alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl,N-alkylsulfamyl, N-arylsulfamyl, arylsulfonyl, N,N-dialkylsulfamyl,N-alkyl-N-arylsulfamyl and heterocyclic;

wherein R² is selected from aryl and heteroaryl, wherein R² isoptionally substituted at a substitutable position with one or moreradicals selected from alkylsulfonyl, sulfamyl, halo, alkyl, alkoxy,hydroxyl and haloalkyl;

wherein R³ is selected from hydrido and alkyl; and

wherein R⁴ is one or more radicals selected from hydrido, halo,alkylthio, alkylsulfinyl, alkyl, alkylsulfonyl, cyano, carboxyl,alkoxycarbonyl, amido, N-alkylaminocarbonyl, N-arylaminocarbonyl,N,N-dialkylaminocarbonyl, N-alkyl-N-arylaminocarbonyl, haloalkyl,hydroxyl, alkoxy, hydroxyalkyl, haloalkoxy, sulfamyl, N-alkylsulfamyl,amino, N-alkylamino, N,N-dialkylamino, heterocyclic, nitro andacylamino;

provided either R⁴ is sulfamyl or alkylsulfonyl, or R² is substitutedwith sulfamyl or alkylsulfonyl;

or a pharmaceutically-acceptable salt thereof.

Compounds of Formula I would be useful for, but not limited to, thetreatment of inflammation in a subject, and for treatment of otherinflammation-associated disorders, such as, as an analgesic in thetreatment of pain and headaches, or as an antipyretic for the treatmentof fever. For example, compounds of Formula I would be useful to treatarthritis, including but not limited to rheumatoid arthritis,spondyloarthopathies, gouty arthritis, osteoarthritis, systemic lupuserythematosus and juvenile arthritis. Such compounds of Formula I wouldbe useful in the treatment of asthma, bronchitis, menstrual cramps,tendinitis, bursitis, and skin related conditions such as psoriasis,eczema, burns and dermatitis. Compounds of Formula I also would beuseful to treat gastrointestinal conditions such as inflammatory boweldisease, Crohn's disease, gastritis, irritable bowel syndrome andulcerative colitis and for the prevention of colorectal cancer.Compounds of Formula I would be useful in treating inflammation in suchdiseases as vascular diseases, migraine headaches, periarteritis nodosa,thyroiditis, aplastic anemia, Hodgkin's disease, sclerodoma, rheumaticfever, type I diabetes, myasthenia gravis, sarcoidosis, nephroticsyndrome, Behcet's syndrome, polymyositis, gingivitis, hypersensitivity,conjunctivitis, swelling occurring after injury, myocardial ischemia,and the like. The compounds are useful as antiinflammatory agents, suchas for the treatment of arthritis, with the additional benefit of havingsignificantly less harmful side effects.

The present invention preferably includes compounds which selectivelyinhibit cyclooxygenase II over cyclooxygenase I. Preferably, thecompounds have a cyclooxygenase II IC₅₀ of less than about 0.2 μM, andalso have a selectivity ratio of cyclooxygenase II inhibition overcyclooxygenase I inhibition of at least 50, and more preferably of atleast 100. Even more preferably, the compounds have a cyclooxygenase IIC₅₀ of greater than about 1 μM, and more preferably of greater than 10μM. Such preferred selectivity may indicate an ability to reduce theincidence of common NSAID-induced side effects.

A preferred class of compounds consists of those compounds of Formula Iwherein A is --(CH₂)_(m) --X--(CH₂)_(n) --;

wherein X is selected from S(O)_(p), O and NR³ ;

wherein m is 0 to 3, inclusive;

wherein n is 0 to 3, inclusive;

wherein p is 0 to 2, inclusive;

wherein B is selected from phenyl, naphthyl and five and six memberedheteroaryl;

wherein R¹ is selected from halo, lower haloalkyl, cyano, nitro, formyl,lower alkoxycarbonyl, lower carboxyalkyl, lower alkoxycarbonylalkyl,amidino, cyanoamidino, lower alkoxy, lower alkoxyalkyl, aminocarbonyl,lower aminocarbonylalkyl, lower N-alkylaminocarbonyl,N-phenylaminocarbonyl, lower N,N-dialkylaminocarbonyl, lowerN-alkyl-N-phenylaminocarbonyl, lower alkylcarbonyl, loweralkylcarbonylalkyl, lower hydroxyalkyl, lower alkylthio, loweralkylsulfinyl, lower alkylsulfonyl, lower alkylthioalkyl, loweralkylsulfinylalkyl, lower alkylsulfonylalkyl, lower N-alkylsulfamyl,N-phenylsulfamyl, phenylsulfonyl, lower N,N-dialkylsulfamyl, lowerN-alkyl-N-phenylsulfamyl and five-seven membered heterocyclic;

wherein R² is selected from phenyl and five or six membered heteroaryl,wherein R² is optionally substituted at a substitutable position withone or more radicals selected from lower alkylsulfonyl, sulfamyl, halo,lower alkyl, lower alkoxy, hydroxyl and lower haloalkyl;

wherein R³ is selected from hydrido and lower alkyl; and

wherein R⁴ is one or more radicals selected from hydrido, halo, loweralkylthio, lower alkylsulfinyl, lower alkyl, lower alkylsulfonyl, cyano,carboxyl, lower alkoxycarbonyl, aminocarbonyl, lowerN-alkylaminocarbonyl, N-phenylaminocarbonyl, lowerN,N-dialkylaminocarbonyl, lower N-alkyl-N-phenylaminocarbonyl, lowerhaloalkyl, hydroxyl, lower alkoxy, lower hydroxyalkyl, lower haloalkoxy,sulfamyl, lower N-alkylsulfamyl, amino, lower N-alkylamino, lowerN,N-dialkylamino, five-seven membered heterocyclic, nitro and acylamino;

or a pharmaceutically-acceptable salt thereof.

A more preferred class of compounds consists of those compounds ofFormula I wherein A is --(CH₂)_(m) --X--(CH₂)_(n) --; wherein X isS(O)_(p) or O; wherein m is 0, 1 or 2; wherein n is 0, 1 or 2; wherein pis 0, 1 or 2; wherein B is selected from phenyl and five and sixmembered heteroaryl; wherein R¹ is selected from halo, lower haloalkyl,cyano, formyl, lower alkoxycarbonyl, aminocarbonyl, loweralkoxycarbonylalkyl, lower alkoxy, lower alkoxyalkyl, loweraminocarbonylalkyl, lower N-alkylaminocarbonyl, N-phenylaminocarbonyl,lower N,N-dialkylaminocarbonyl, lower N-alkyl-N-phenylaminocarbonyl andlower hydroxyalkyl; wherein R² is phenyl substituted at a substitutableposition with a radical selected from lower alkylsulfonyl and sulfamyl;and wherein R⁴ is one or more radicals selected from hydrido, halo,lower alkylthio, lower alkylsulfinyl, lower alkyl, lower alkylsulfonyl,cyano, carboxyl, lower alkoxycarbonyl, aminocarbonyl, lowerN-alkylaminocarbonyl, lower N,N-dialkylaminocarbonyl, lowerN-alkyl-N-phenylaminocarbonyl, lower haloalkyl, hydroxyl, lower alkoxy,lower hydroxyalkyl, amino, lower N-alkylamino, lower N,N-dialkylamino,lower haloalkoxy and nitro; or a pharmaceutically-acceptable saltthereof.

An even more preferred class of compounds consists of those compounds ofFormula I wherein A is --(CH₂)_(m) --X--(CH₂)_(n) --; wherein X isS(O)_(p) or O; wherein m is 0 or 1; wherein n is 0 or 1; wherein p is 0or 1; wherein B is selected from phenyl and five and six memberedheteroaryl; wherein R¹ is selected from lower haloalkyl, cyano, formyl,lower alkoxycarbonyl, lower alkoxy, lower N-alkylaminocarbonyl,N-phenylaminocarbonyl, lower N,N-dialkylaminocarbonyl and lowerN-alkyl-N-phenylaminocarbonyl; wherein R² is phenyl substituted at asubstitutable position with a radical selected from lower alkylsulfonyland sulfamyl; and wherein R⁴ is one or more radicals selected fromhydrido, halo, lower alkylthio, lower alkylsulfinyl, lower alkyl, cyano,carboxyl, lower alkoxycarbonyl, aminocarbonyl, lower haloalkyl,hydroxyl, lower alkoxy, amino, lower N-alkylamino, lowerN,N-dialkylamino, lower hydroxyalkyl and lower haloalkoxy; or apharmaceutically-acceptable salt thereof.

A class of compounds of particular interest consists of those compoundsof Formula I wherein A is --(CH₂)_(m) --X--(CH₂)_(n) --; wherein X isS(O)_(p) or O; wherein m is 0 or 1; wherein n is 0 or 1; wherein p is 0or 1; wherein B is selected from phenyl, thienyl, pyridyl, furyl,oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl,triazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl,thiaimidazolyl, oxoimidazolyl, azaoxazolyl, azathiazolyl and pyrrolyl;

wherein R¹ is selected from fluoromethyl, difluoromethyl,trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl,pentafluoroethyl, heptafluoropropyl, difluorochloromethyl,dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl,dichloropropyl, cyano, formyl, carboxyl, methoxycarbonyl,ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl,propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, pentoxycarbonyl,aminocarbonyl, methoxy, ethoxy, propoxy, n-butoxy,N-methylaminocarbonyl, N-phenylaminocarbonyl, N,N-dimethylaminocarbonyl,N-methyl-N-phenylaminocarbonyl and methylcarbonyl;

wherein R² is phenyl substituted at a substitutable position with aradical selected from methylsulfonyl and sulfamyl; and

wherein R⁴ is optionally substituted with one or more radicals selectedfrom hydrido, fluoro, chloro, bromo, methylthio, ethylthio,isopropylthio, tert-butylthio, isobutylthio, hexylthio, methylsulfinyl,ethylsulfinyl, isopropylsulfinyl, tert-butylsulfinyl, isobutylsulfinyl,hexylsulfinyl, methyl, ethyl, isopropyl, tert-butyl, isobutyl, hexyl,cyano, carboxyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl,tert-butoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl,pentoxycarbonyl, aminocarbonyl, fluoromethyl, difluoromethyl,trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl,pentafluoroethyl, heptafluoropropyl, difluorochloromethyl,dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl,dichloropropyl, hydroxyl, methoxy, methylenedioxy, ethoxy, propoxy,n-butoxy, hydroxymethyl and trifluoromethoxy; or apharmaceutically-acceptable salt thereof.

The preferred compounds of Formula I can be represented by FormulasIa-Ih as follows: ##STR3##

A family of specific compounds of particular interest within Formula Iconsists of compounds and pharmaceutically-acceptable salts thereof asshown in the following Tables:

                  TABLE I                                                         ______________________________________                                        General Structure 1a                                                          R.sup.1       R.sup.2      R.sup.4                                            ______________________________________                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.2 Cl   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.2 CF.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CO.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CO.sub.2 CH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CO.sub.2 C.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CONH.sub.2    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CONHCH.sub.3  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CONH(C.sub.6 H.sub.3)                                                                       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(CH.sub.3).sub.2                                                                         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(C.sub.2 H.sub.5).sub.2                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(CH.sub.3)(C.sub.2 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(CH.sub.3)(C.sub.6 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                   ##STR4##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                   ##STR5##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CN            C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OH   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SOCH.sub.3                                                                         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SOC.sub.2 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SOC.sub.6 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SO.sub.2 CH.sub.3                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.2 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.6 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          5-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6,7-(OCH.sub.2 O)                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-N(CH.sub.3).sub.2                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-OCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          5-F, 6-OCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          5-Cl, 6-OCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-Cl, 5-F                                          CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-CH.sub.3                                         CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          5-F, 6-CH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          5,6-F                                              CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-SCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          5-F, 6-SCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-SOCH.sub.3                                       CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          5-F, 6-SOCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          5-F, 6-CH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 F                                                                          6-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 Cl                                                                         6-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 OCH.sub.3                                                                  6-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 CH.sub.3                                                                   6-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 SOCH.sub.3                                                                 6-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.2 Cl   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.2 CF.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CO.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CO.sub.2 CH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CO.sub.2 C.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CONH.sub.2    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CONHCH.sub.3  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CONH(C.sub.6 H.sub.3)                                                                       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(CH.sub.3).sub.2                                                                         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(C.sub.2 H.sub.5).sub.2                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(CH.sub.3)(C.sub.2 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(CH.sub.3)(C.sub.6 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                   ##STR6##     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                   ##STR7##     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CN            C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OH   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SOCH.sub.3                                                                         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SOC.sub.6 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SO.sub.2 CH.sub.3                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.2 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.6 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          5-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6,7-(OCH.sub.2 O)                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-N(CH.sub.3).sub.2                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-OCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          5-F, 6-OCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          5-Cl, 6-OCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-Cl, 5-F                                          CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-CH.sub.3                                         CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          5-F, 6-CH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          5,6-F                                              CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-SCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          5-F, 6-SCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-SOCH.sub.3                                       CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          5-F, 6-SOCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          5-F, 6-CH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 F                                                                          6-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 Cl                                                                         6-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 OCH.sub.3                                                                  6-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 CH.sub.3                                                                   6-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 SOCH.sub.3                                                                 6-SO.sub.2 NH.sub.2                                CF.sub.3      thienylSO.sub.2 NH.sub.2                                                                   5-F, 6-OCH.sub.3                                   ______________________________________                                    

                  TABLE II                                                        ______________________________________                                        General Structure Ib                                                          B                   R.sup.2                                                   ______________________________________                                         ##STR8##           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR9##           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR10##          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR11##          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR12##          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR13##          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR14##          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR15##          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR16##          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR17##          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR18##          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR19##          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR20##          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR21##          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR22##          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR23##          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR24##          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR25##          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR26##          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR27##          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                         ______________________________________                                    

                  TABLE III                                                       ______________________________________                                        General Structure Ic                                                          R.sup.1       R.sup.2      R.sup.4                                            ______________________________________                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.2 Cl   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.2 CF.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CO.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CO.sub.2 CH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CO.sub.2 C.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CONH.sub.2    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CONHCH.sub.3  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CONH(C.sub.6 H.sub.3)                                                                       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(CH.sub.3).sub.2                                                                         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(C.sub.2 H.sub.5).sub.2                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(CH.sub.3)(C.sub.2 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(CH.sub.3)(C.sub.6 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                   ##STR28##    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                   ##STR29##    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CN            C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OH   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SOCH.sub.3                                                                         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SOC.sub.2 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SOC.sub.6 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SO.sub.2 CH.sub.3                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.2 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.6 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          5-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6,7-(OCH.sub.2 O)                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-N(CH.sub.3).sub.2                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-OCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          5-F, 6-OCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          5-Cl, 6-OCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-Cl, 5-F                                          CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-CH.sub.3                                         CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          5-F, 6-CH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          5,6-F                                              CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-SCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          5-F, 6-SCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-SOCH.sub.3                                       CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          5-F, 6-SOCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          5-F, 6-CH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 F                                                                          6-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 Cl                                                                         6-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 OCH.sub.3                                                                  6-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 CH.sub.3                                                                   6-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 SOCH.sub.3                                                                 6-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.2 Cl   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.2 CF.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CO.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CO.sub.2 CH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CO.sub.2 C.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CONH.sub.2    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CONHCH.sub.3  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CONH(C.sub.6 H.sub.3)                                                                       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(CH.sub.3).sub.2                                                                         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(C.sub.2 H.sub.5).sub.2                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(CH.sub.3)(C.sub.2 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(CH.sub.3)(C.sub.6 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                   ##STR30##    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                   ##STR31##    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CN            C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OH   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SOC.sub.6 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SO.sub.2 CH.sub.3                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.2 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.6 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          5-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6,7-(OCH.sub.2 O)                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-N(CH.sub.3).sub.2                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-OCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          5-F, 6-OCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          5-Cl, 6-OCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-Cl, 5-F                                          CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-CH.sub.3                                         CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          5-F, 6-CH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          5,6-F                                              CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-SCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          5-F, 6-SCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-SOCH.sub.3                                       CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          5-F, 6-SOCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          5-F, 6-CH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 F                                                                          6-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 Cl                                                                         6-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 OCH.sub.3                                                                  6-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 CH.sub.3                                                                   6-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 SOCH.sub.3                                                                 6-SO.sub.2 NH.sub.2                                CF.sub.3      thienylSO.sub.2 NH.sub.2                                                                   5-F, 6-OCH.sub.3                                   ______________________________________                                    

                  TABLE IV                                                        ______________________________________                                        General Structure Id                                                          B              R.sup.2                                                        ______________________________________                                         ##STR32##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                               ##STR33##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                               ##STR34##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                               ##STR35##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                               ##STR36##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                               ##STR37##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                               ##STR38##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                               ##STR39##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                               ##STR40##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                               ##STR41##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                               ##STR42##     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                               ##STR43##     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                               ##STR44##     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                               ##STR45##     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                               ##STR46##     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                               ##STR47##     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                               ##STR48##     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                               ##STR49##     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                               ##STR50##     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                               ##STR51##     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                              ______________________________________                                    

                  TABLE V                                                         ______________________________________                                        General Structure Ie                                                          R.sup.1       R.sup.2       R.sup.4                                           ______________________________________                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CF.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CF.sub.2 Cl   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CF.sub.2 CF.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CO.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CO.sub.2 CH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CO.sub.2 C.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CONH.sub.2    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CONHCH.sub.3  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CONH(C.sub.6 H.sub.3)                                                                       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CON(CH.sub.3).sub.2                                                                         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CON(C.sub.2 H.sub.5).sub.2                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CON(CH.sub.3)(C.sub.2 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CON(CH.sub.3)(C.sub.6 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                  ##STR52##    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                  ##STR53##    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CN            C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CH.sub.2 OH   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CH.sub.2 OCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CH.sub.2 OC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CH.sub.2 OC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CH.sub.2 SCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CH.sub.2 SC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CH.sub.2 SC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CH.sub.2 SOCH.sub.3                                                                         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CH.sub.2 SOC.sub.2 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CH.sub.2 SOC.sub.6 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CH.sub.2 SO.sub.2 CH.sub.3                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CH.sub.2 SO.sub.2 C.sub.2 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CH.sub.2 SO.sub.2 C.sub.6 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           H                                                 CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           6-F                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           7-F                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           8-F                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           7-Cl                                              CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           8-Cl                                              CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           7,8-(OCH.sub.2 O)                                 CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           7-N(CH.sub.3).sub.2                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           7-OCH.sub.3                                       CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           6-F, 7-OCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           6-Cl, 7-OCH.sub.3                                 CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           7-Cl, 6-F                                         CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           7-CH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           6-F, 7-CH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           6,7-F                                             CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           7-SCH.sub.3                                       CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           6-F, 7-SCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           7-SOCH.sub.3                                      CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           6-F, 7-SOCH.sub.3                                 CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                           6-F, 7-CH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 F                                                                           7-SO.sub.2 CH.sub.3                               CF.sub.3      C.sub.6 H.sub.5 Cl                                                                          7-SO.sub.2 CH.sub.3                               CF.sub.3      C.sub.6 H.sub.5 OCH.sub.3                                                                   7-SO.sub.2 CH.sub.3                               CF.sub.3      C.sub.6 H.sub.5 CH.sub.3                                                                    7-SO.sub.2 CH.sub.3                               CF.sub.3      C.sub.6 H.sub.5 SOCH.sub.3                                                                  7-SO.sub.2 CH.sub.3                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CF.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CF.sub.2 Cl   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CF.sub.2 CF.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CO.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CO.sub.2 CH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CO.sub.2 C.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CONH.sub.2    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CONHCH.sub.3  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CONH(C.sub.6 H.sub.3)                                                                       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CON(CH.sub.3).sub.2                                                                         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CON(C.sub.2 H.sub.5).sub.2                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CON(CH.sub.3)(C.sub.2 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CON(CH.sub.3)(C.sub.6 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                  ##STR54##    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                  ##STR55##    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CN            C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CH.sub.2 OH   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CH.sub.2 OCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CH.sub.2 OC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CH.sub.2 OC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CH.sub.2 SCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CH.sub.2 SC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CH.sub.2 SC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CH.sub.2 SOCH.sub.3                                                                         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CH.sub.2 SOC.sub.2 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CH.sub.2 SOC.sub.6 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CH.sub.2 SO.sub.2 CH.sub.3                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CH.sub.2 SO.sub.2 C.sub.2 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CH.sub.2 SO.sub.2 C.sub.6 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           H                                                 CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           6-F                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           7-F                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           8-F                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           7-Cl                                              CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           8-Cl                                              CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           7,8-(OCH.sub.2 O)                                 CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           7-N(CH.sub.3).sub.2                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           7-OCH.sub.3                                       CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           6-F, 7-OCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           6-Cl, 7-OCH.sub.3                                 CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           7-Cl, 6-F                                         CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           7-CH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           6-F, 7-CH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           6,7-F                                             CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           7-SCH.sub.3                                       CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           6-F, 7-SCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           7-SOCH.sub.3                                      CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           6-F, 7-SOCH.sub.3                                 CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           6-F, 7-CH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                           6-F, 7-OCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 F                                                                           7-SO.sub.2 NH.sub.2                               CF.sub.3      C.sub.6 H.sub.5 Cl                                                                          7-SO.sub.2 NH.sub.2                               CF.sub.3      C.sub.6 H.sub.5 OCH.sub.3                                                                   7-SO.sub.2 NH.sub.2                               CF.sub.3      C.sub.6 H.sub.5 CH.sub.3                                                                    7-SO.sub.2 NH.sub.2                               CF.sub.3      C.sub.6 H.sub.5 SOCH.sub.3                                                                  7-SO.sub.2 NH.sub.2                               ______________________________________                                    

                  TABLE VI                                                        ______________________________________                                        General Structure If                                                          B               R.sup.2                                                       ______________________________________                                         ##STR56##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR57##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR58##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR59##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR60##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR61##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR62##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR63##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR64##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR65##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR66##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR67##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR68##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR69##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR70##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR71##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR72##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR73##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR74##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR75##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR76##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR77##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR78##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR79##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR80##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR81##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR82##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR83##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR84##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR85##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR86##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR87##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR88##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR89##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR90##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR91##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR92##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR93##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR94##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR95##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR96##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR97##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR98##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR99##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR100##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR101##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR102##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                              ##STR103##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                             ______________________________________                                    

                  TABLE VII                                                       ______________________________________                                        General Structure Ig                                                          R.sup.1       R.sup.2      R.sup.4                                            ______________________________________                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.2 Cl   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.2 CF.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CO.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CO.sub.2 CH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CO.sub.2 C.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CONH.sub.2    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CONHCH.sub.3  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CONH(C.sub.6 H.sub.3)                                                                       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(CH.sub.3).sub.2                                                                         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(C.sub.2 H.sub.5).sub.2                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(CH.sub.3)(C.sub.2 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(CH.sub.3)(C.sub.6 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                   ##STR104##   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                   ##STR105##   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CN            C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OH   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SOCH.sub.3                                                                         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SOC.sub.2 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SOC.sub.6 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SO.sub.2 CH.sub.3                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.2 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.6 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7,8-(OCH.sub.2 O)                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-N(CH.sub.3).sub.2                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-OCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F, 7-OCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-Cl, 7-OCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-Cl, 6-F                                          CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-CH.sub.3                                         CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F, 7-CH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6,7-F                                              CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-SCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F, 7-SCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-SOCH.sub.3                                       CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F, 7-SOCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F, 7-CH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 F                                                                          7-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 Cl                                                                         7-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 OCH.sub.3                                                                  7-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 CH.sub.3                                                                   7-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 SONH.sub.3                                                                 7-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.2 Cl   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.2 CF.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CO.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CO.sub.2 CH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CO.sub.2 C.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CONH.sub.2    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CONHCH.sub.3  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CONH(C.sub.6 H.sub.3)                                                                       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(CH.sub.3).sub.2                                                                         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(C.sub.2 H.sub.5).sub.2                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(CH.sub.3)(C.sub.2 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(CH.sub.3)(C.sub.6 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                   ##STR106##   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                   ##STR107##   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CN            C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OH   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SOCH.sub.3                                                                         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SOC.sub.2 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SOC.sub.6 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SO.sub.2 CH.sub.3                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.2 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SO.sub.2 C6H.sub.5                                                                 C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7,8-(OCH.sub.2 O)                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-N(CH.sub.3).sub.2                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-OCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-OCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-Cl, 7-OCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-Cl, 6-F                                          CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-CH.sub.3                                         CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-CH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6,7-F                                              CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-SCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-SCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-SOCH.sub.3                                       CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-SOCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-CH.sub.3                                    CF.sub.3      thienylSO.sub.2 NH.sub.2                                                                   6-F, 7-OCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 F                                                                          7-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 Cl                                                                         7-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 OCH.sub.3                                                                  7-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 CH.sub.3                                                                   7-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 SOCH.sub.3                                                                 7-SO.sub.2 NH.sub.2                                ______________________________________                                    

                  TABLE VIII                                                      ______________________________________                                        General Structure Ih                                                          B                   R.sup.2                                                   ______________________________________                                         ##STR108##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR109##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR110##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR111##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR112##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR113##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR114##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR115##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR116##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR117##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR118##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR119##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR120##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR121##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR122##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR123##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR124##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR125##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR126##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR127##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR128##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR129##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR130##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR131##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR132##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR133##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR134##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR135##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR136##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR137##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR138##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR139##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR140##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR141##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR142##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR143##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR144##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR145##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR146##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR147##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR148##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR149##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR150##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR151##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR152##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR153##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR154##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR155##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                         ______________________________________                                    

                  TABLE IX                                                        ______________________________________                                        General Structure Ii                                                          p   R.sup.1        R.sup.2      R.sup.4                                       ______________________________________                                        0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CF.sub.2 H     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CF.sub.2 Cl    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CF.sub.2 CF.sub.3                                                                            C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CO.sub.2 H     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CO.sub.2 CH.sub.3                                                                            C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CO.sub.2 C.sub.2 H.sub.5                                                                     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CONH.sub.2     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CONHCH.sub.3   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CONH(C.sub.6 H.sub.3)                                                                        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CON(CH.sub.3).sub.2                                                                          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CON(C.sub.2 H.sub.5).sub.2                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CON(CH.sub.3)(C.sub.2 H.sub.5)                                                               C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CON(CH.sub.3)(C.sub.6 H.sub.5)                                                               C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  ##STR156##    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  ##STR157##    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CN             C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CH.sub.2 OH    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CH.sub.2 OCH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CH.sub.2 OC.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CH.sub.2 OC.sub.6 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CH.sub.2 SCH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CH.sub.2 SC.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CH.sub.2 SC.sub.6 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CH.sub.2 SOCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CH.sub.2 SOC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CH.sub.2 SOC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CH.sub.2 SO.sub.2 CH.sub.3                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CH.sub.2 SO.sub.2 C.sub.2 H.sub.5                                                            C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CH.sub.2 SO.sub.2 C.sub.6 H.sub.5                                                            C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                             0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F                                           0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-F                                           0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-F                                           0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-Cl                                          0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-Cl                                          0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7,8-(OCH.sub.2 O)                             0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-N(CH.sub.3).sub.2                           0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-OCH.sub.3                                   0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F, 7-OCH.sub.3                              0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-Cl, 7-OCH.sub.3                             0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-Cl, 6-F                                     0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-CH.sub.3                                    0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F, 7-CH.sub.3                               0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6,7-F                                         0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-SCH.sub.3                                   0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F, 7-SCH.sub.3                              0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-SOCH.sub.3                                  0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F, 7-SOCH.sub.3                             0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F, 7-CH.sub.3                               0   CF.sub.3       C.sub.6 H.sub.5 F                                                                          7-SO.sub.2 CH.sub.3                           0   CF.sub.3       C.sub.6 H.sub.5 Cl                                                                         7-SO.sub.2 CH.sub.3                           0   CF.sub.3       C.sub.6 H.sub.5 OCH.sub.3                                                                  7-SO.sub.2 CH.sub.3                           0   CF.sub.3       C.sub.6 H.sub.5 CH.sub.3                                                                   7-SO.sub.2 CH.sub.3                           0   CF.sub.3       C.sub.6 H.sub.5 SOCH.sub.3                                                                 7-SO.sub.2 CH.sub.3                           0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CF.sub.2 H     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CF.sub.2 Cl    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CF.sub.2 CF.sub.3                                                                            C.sub.6 H.sub.5 SO.sub.2 NH                                                                H                                             0   CO.sub.2 H     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CO.sub.2 CH.sub.3                                                                            C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CO.sub.2 C.sub.2 H.sub.5                                                                     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CONH.sub.2     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CONHCH.sub.3   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CONH(C.sub.6 H.sub.3)                                                                        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CON(CH.sub.3).sub.2                                                                          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CON(C.sub.2 H.sub.5).sub.2                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CON(CH.sub.3)(C.sub.2 H.sub.5)                                                               C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CON(CH.sub.3)(C.sub.6 H.sub.5)                                                               C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  ##STR158##    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  ##STR159##    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CN             C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CH.sub.2 OH    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CH.sub.2 OCH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CH.sub.2 OC.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CH.sub.2 OC.sub.6 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CH.sub.2 SCH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CH.sub.2 SC.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CH.sub.2 SC.sub.6 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CH.sub.2 SOCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CH.sub.2 SOC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CH.sub.2 SOC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CH.sub.2 SO.sub.2 CH.sub.3                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CH.sub.2 SO.sub.2 C.sub.2 H.sub.5                                                            C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CH.sub.2 SO.sub.2 C.sub.6 H.sub.5                                                            C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                             0   CONH.sub.2     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F                                           0   CO.sub.2 CH.sub.3                                                                            C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F                                           0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F                                           0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F                                           0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-F                                           0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-Cl                                          0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-Cl                                          0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7,8-(OCH.sub.2 O)                             0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-N(CH.sub.3).sub.2                           0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-OCH.sub.3                                   0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-OCH.sub.3                              0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-Cl, 7-OCH.sub.3                             0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-Cl, 6-F                                     0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-CH.sub.3                                    0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-CH.sub.3                               0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6,7-F                                         0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-SCH.sub.3                                   0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-SCH.sub.3                              0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-SOCH.sub.3                                  0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-SOCH.sub.3                             0   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-Cl, 7-CH.sub.3                              0   CF.sub.3       thienylSO.sub.2 NH.sub.2                                                                   6-F, 7-OCH.sub.3                              0   CF.sub.3       C.sub.6 H.sub.5 F                                                                          7-SO.sub.2 NH.sub.2                           0   CF.sub.3       C.sub.6 H.sub.5 Cl                                                                         7-SO.sub.2 NH.sub.2                           0   CF.sub.3       C.sub.6 H.sub.5 OCH.sub.3                                                                  7-SO.sub.2 NH.sub.2                           0   CF.sub.3       C.sub.6 H.sub.5 CH.sub.3                                                                   7-SO.sub.2 NH.sub.2                           0   CF.sub.3       C.sub.6 H.sub.5 SOCH.sub.3                                                                 7-SO.sub.2 NH.sub.2                           0   CHF.sub.2      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-OCH.sub.3                              1   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-OCH.sub.3                              1   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-Cl, 7-OCH.sub.3                             1   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-Cl, 6-F                                     1   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-CH.sub.3                               1   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6,7-F                                         1   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-SCH.sub.3                              1   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-SOCH.sub.3                             1   CF.sub.3       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-Cl, 7-CH.sub.3                              ______________________________________                                    

                  TABLE X                                                         ______________________________________                                        General Structure Ij                                                          B                R.sup.2      p                                               ______________________________________                                         ##STR160##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR161##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR162##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR163##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR164##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR165##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR166##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR167##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR168##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR169##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR170##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR171##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR172##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR173##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR174##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR175##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR176##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR177##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR178##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR179##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR180##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR181##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR182##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR183##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.2                                                          0                                                ##STR184##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR185##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR186##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR187##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR188##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR189##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR190##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR191##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR192##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR193##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR194##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR195##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR196##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR197##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR198##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR199##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR200##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR201##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR202##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR203##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR204##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR205##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR206##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR207##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          0                                                ##STR208##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          1                                               ______________________________________                                    

                  TABLE XI                                                        ______________________________________                                        General Structure Ik                                                          p   R.sup.1         R.sup.2      R.sup.4                                      ______________________________________                                        0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CF.sub.2 H      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CF.sub.2 Cl     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CF.sub.2 CF.sub.3                                                                             C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CO.sub.2 H      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CO.sub.2 CH.sub.3                                                                             C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CO.sub.2 C.sub.2 H.sub.5                                                                      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CONH.sub.2      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CONHCH.sub.3    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CONH(C.sub.6 H.sub.3)                                                                         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CON(CH.sub.3).sub.2                                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CON(C.sub.2 H.sub.5).sub.2                                                                    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CON(CH.sub.3)(C.sub.2 H.sub.5)                                                                C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CON(CH.sub.3)(C.sub.6 H.sub.5)                                                                C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                 ##STR209##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                 ##STR210##     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CN              C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CH.sub.2 OH     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CH.sub.2 OCH.sub.3                                                                            C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CH.sub.2 OC.sub.2 H.sub.5                                                                     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CH.sub.2 OC.sub.6 H.sub.5                                                                     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CH.sub.2 SCH.sub.3                                                                            C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CH.sub.2 SC.sub.2 H.sub.5                                                                     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CH.sub.2 SC.sub.6 H.sub.5                                                                     C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CH.sub.2 SOCH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CH.sub.2 SOC.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CH.sub.2 SOC.sub.6 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CH.sub.2 SO.sub.2 CH.sub.3                                                                    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CH.sub.2 SO.sub.2 C.sub.2 H.sub.5                                                             C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CH.sub.2 SO.sub.2 C.sub.6 H.sub.5                                                             C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                            0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F                                          0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-F                                          0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-F                                          0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-Cl                                         0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-Cl                                         0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7,8-(OCH.sub.2 O)                            0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-N(CH.sub.3).sub.2                          0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-OCH.sub.3                                  0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F, 7-OCH.sub.3                             0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-Cl, 7-OCH.sub.3                            0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-Cl, 6-F                                    0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-CH.sub.3                                   0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F, 7-CH.sub.3                              0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6,7-F                                        0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-SCH.sub.3                                  0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F, 7-SCH.sub.3                             0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-SOCH.sub.3                                 0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F, 7-SOCH.sub.3                            0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          6-F, 7-CH.sub.3                              0   CF.sub.3        C.sub.6 H.sub.5 F                                                                          7-SO.sub.2 CH.sub.3                          0   CF.sub.3        C.sub.6 H.sub.5 Cl                                                                         7-SO.sub.2 CH.sub.3                          0   CF.sub.3        C.sub.6 H.sub.5 OCH.sub.3                                                                  7-SO.sub.2 CH.sub.3                          0   CF.sub.3        C.sub.6 H.sub.5 CH.sub.3                                                                   7-SO.sub.2 CH.sub.3                          0   CF.sub.3        C.sub.6 H.sub.5 SOCH.sub.3                                                                 7-SO.sub.2 CH.sub.3                          0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CF.sub.2 H      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CF.sub.2 Cl     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CF.sub.2 CF.sub.3                                                                             C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CO.sub.2 H      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CO.sub.2 CH.sub.3                                                                             C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CO.sub.2 C.sub.2 H.sub.5                                                                      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CONH.sub.2      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CONHCH.sub.3    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CONH(C.sub.6 H.sub.3)                                                                         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CON(CH.sub.3).sub.2                                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CON(C.sub.2 H.sub.5).sub.2                                                                    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CON(CH.sub.3)(C.sub.2 H.sub.5)                                                                C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CON(CH.sub.3)(C.sub.6 H.sub.5)                                                                C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                 ##STR211##     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                 ##STR212##     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CN              C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CH.sub.2 OH     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CH.sub.2 OCH.sub.3                                                                            C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CH.sub.2 OC.sub.2 H.sub.5                                                                     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CH.sub.2 OC.sub.6 H.sub.5                                                                     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CH.sub.2 SCH.sub.3                                                                            C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CH.sub.2 SC.sub.2 H.sub.5                                                                     C.sub.6 .sub.5 SO.sub.2 NH.sub.2                                                           H                                            0   CH.sub.2 SC.sub.6 H.sub.5                                                                     C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CH.sub.2 SOCH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CH.sub.2 SOC.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CH.sub.2 SOC.sub.6 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CH.sub.2 SO.sub.2 CH.sub.3                                                                    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CH.sub.2 SO.sub.2 C.sub.2 H.sub.5                                                             C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CH.sub.2 SO.sub.2 C.sub.2 H.sub.5                                                             C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CH.sub.2 SO.sub.2 C.sub.6 H.sub.5                                                             C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                            0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F                                          0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F                                          0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-F                                          0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-Cl                                         0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-Cl                                         0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7,8-(OCH.sub.2 O)                            0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-N(CH.sub.3).sub.2                          0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-OCH.sub.3                                  0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7,8-OCH.sub.3                                0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-OCH.sub.3                             0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-Cl, 7-OCH.sub.3                            0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-Cl, 6-F                                    0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-CH(CH.sub.3).sub.2                         0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-CH.sub.3                                   0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-CH.sub.3                              0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6,7-F                                        0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6,7-Cl                                       0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-SCH.sub.3                                  0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-SCH.sub.3                             0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-SOCH.sub.3                                 0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-SOCH.sub.3                            0   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-Cl, 7-CH.sub.3                             0   CF.sub.3                                                                  thienylSO.sub.2 NH.sub.2                                                          6-F, 7-OCH.sub.3                                                          0   CF.sub.3        C.sub.2 H.sub.5 F                                                                          7-SO.sub.2 NH.sub.2                          0   CF.sub.3        C.sub.6 H.sub.5 Cl                                                                         7-SO.sub.2 NH.sub.2                          0   CF.sub.3        C.sub.6 H.sub.5 OCH.sub.3                                                                  7-SO.sub.2 NH.sub.2                          0   CF.sub.3        C.sub.6 H.sub.5 CH.sub.3                                                                   7-SO.sub.2 NH.sub.2                          0   CF.sub.3        C.sub.6 H.sub.5 SOCH.sub.3                                                                 7-SO.sub.2 NH.sub.2                          1   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-OCH.sub.3                             1   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-Cl, 7-OCH.sub.3                            1   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-Cl, 6-F                                    1   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-CH.sub.3                              1   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6,7-F                                        1   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-SCH.sub.3                             1   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-F, 7-SOCH.sub.3                            1   CF.sub.3        C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          6-Cl, 7-CH.sub.3                             ______________________________________                                    

                  TABLE XII                                                       ______________________________________                                        General Structure Il                                                          B                R.sup.2      p                                               ______________________________________                                         ##STR213##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR214##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR215##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR216##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR217##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR218##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR219##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR220##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR221##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR222##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR223##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR224##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR225##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR226##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR227##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR228##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR229##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR230##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR231##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR232##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR233##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR234##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR235##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR236##      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          0                                                ##STR237##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR238##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR239##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR240##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR241##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR242##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR243##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR244##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR245##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR246##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR247##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR248##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR249##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR250##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR251##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR252##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR253##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR254##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR255##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR256##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR257##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR258##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR259##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                                ##STR260##      C.sub.6 H.sub.5 SO.sub.2 NH.sub.3                                                          0                                               ______________________________________                                    

                  TABLE XIII                                                      ______________________________________                                        General Structure Im                                                          R.sup.1       R.sup.2      R.sup.4                                            ______________________________________                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.2 Cl   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.2 CF.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CO.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CO.sub.2 CH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CO.sub.2 C.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CONH.sub.2    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CONHCH.sub.3  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CONH(C.sub.6 H.sub.3)                                                                       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(CH.sub.3).sub.2                                                                         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(C.sub.2 H.sub.5).sub.2                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(CH.sub.3)(C.sub.2 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(CH.sub.3)(C.sub.6 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                   ##STR261##   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                   ##STR262##   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CN            C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OH   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SOCH.sub.3                                                                         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SOC.sub.2 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SOC.sub.6 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SO.sub.2 CH.sub.3                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.2 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.6 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          9-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          9-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8,9-(OCH.sub.2 O)                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-N(CH.sub.3).sub.2                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-OCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-F, 8-OCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-Cl, 8-OCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-Cl, 7-F                                          CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-CH.sub.3                                         CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-F, 8-CH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7,8-F                                              CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-SCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-F, 8-SCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-SOCH.sub.3                                       CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-F, 8-SOCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-F, 8-CH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 F                                                                          8-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 Cl                                                                         8-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 OCH.sub.3                                                                  8-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 CH.sub.3                                                                   8-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 SOCH.sub.3                                                                 8-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.2 Cl   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.2 CF.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CO.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CO.sub.2 CH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CO.sub.2 C.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CONH.sub.2    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CONHCH.sub.3  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CONH(C.sub.6 H.sub.3)                                                                       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(CH.sub.3).sub.2                                                                         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(C.sub.2 H.sub.5).sub.2                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(CH.sub.3)(C.sub.2 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(CH.sub.3)(C.sub.6 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                   ##STR263##   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                   ##STR264##   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CN            C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OH   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SOCH.sub.3                                                                         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SOC.sub.2 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SOC.sub.6 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SO.sub.2 CH.sub.3                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.2 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.6 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          9-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7,8-(OCH.sub.2 O)                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-N(CH.sub.3).sub.2                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-OCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F, 8-OCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-Cl, 8-OCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-Cl, 7-F                                          CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-CH.sub.3                                         CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F, 8-CH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7,8-F                                              CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-SCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F, 8-SCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-SOCH.sub.3                                       CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F, 8-SOCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F, 8-CH.sub.3                                    CF.sub.3      thienylSO.sub.2 NH.sub.2                                                                   7-F, 8-OCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 F                                                                          8-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 Cl                                                                         8-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 OCH.sub.3                                                                  8-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 CH.sub.3                                                                   8-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 SOCH.sub.3                                                                 8-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          9-Cl                                               ______________________________________                                    

                  TABLE XIV                                                       ______________________________________                                        General Structure In                                                          B                   R.sup.2                                                   ______________________________________                                         ##STR265##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR266##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR267##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR268##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR269##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR270##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR271##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR272##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR273##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR274##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR275##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR276##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR277##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR278##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR279##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR280##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR281##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR282##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR283##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR284##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                         ______________________________________                                    

                  TABLE XV                                                        ______________________________________                                        General Structure Io                                                          R.sup.1       R.sup.2      R.sup.4                                            ______________________________________                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.2 Cl   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.2 CF.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CO.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CO.sub.2 CH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CO.sub.2 C.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CONH.sub.2    C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CONHCH.sub.3  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CONH(C.sub.6 H.sub.3)                                                                       C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(CH.sub.3).sub.2                                                                         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(C.sub.2 H.sub.5).sub.2                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(CH.sub.3)(C.sub.2 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CON(CH.sub.3)(C.sub.6 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                   ##STR285##   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                   ##STR286##   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CN            C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OH   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 OC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SOCH.sub.3                                                                         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SOC.sub.2 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SOC.sub.6 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SO.sub.2 CH.sub.3                                                                  C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.2 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.6 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          H                                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          9-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          9-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8,9-(OCH.sub.2 O)                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-N(CH.sub.3).sub.2                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-OCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-F, 8-OCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-Cl, 8-OCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-Cl, 7-F                                          CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-CH.sub.3                                         CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-F, 8-CH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7,8-F                                              CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-SCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-F, 8-SCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          8-SOCH.sub.3                                       CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-F, 8-SOCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                                                          7-F, 8-CH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 F                                                                          8-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 Cl                                                                         8-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 OCH.sub.3                                                                  8-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 CH.sub.3                                                                   8-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 SOCH.sub.3                                                                 8-SO.sub.2 CH.sub.3                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.2 Cl   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.2 CF.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CO.sub.2 H    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CO.sub.2 CH.sub.3                                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CO.sub.2 C.sub.2 H.sub.5                                                                    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CONH.sub.2    C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CONHCH.sub.3  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CONH(C.sub.6 H.sub.3)                                                                       C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(CH.sub.3).sub.2                                                                         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(C.sub.2 H.sub.5).sub.2                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(CH.sub.3)(C.sub.2 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CON(CH.sub.3)(C.sub.6 H.sub.5)                                                              C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                   ##STR287##   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                   ##STR288##   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CN            C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OH   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 OC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SCH.sub.3                                                                          C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SC.sub.2 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SC.sub.6 H.sub.5                                                                   C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SOCH.sub.3                                                                         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SOC.sub.2 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SOC.sub.6 H.sub.5                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SO.sub.2 CH.sub.3                                                                  C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.2 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CH.sub.2 SO.sub.2 C.sub.6 H.sub.5                                                           C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          H                                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          9-F                                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          9-Cl                                               CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7,8-(OCH.sub.2 O)                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-N(CH.sub.3).sub.2                                CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-OCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F, 8-OCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-Cl, 8-OCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-Cl, 7-F                                          CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-CH.sub.3                                         CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F, 8-CH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7,8-F                                              CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-SCH.sub.3                                        CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F, 8-SCH.sub.3                                   CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          8-SOCH.sub.3                                       CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F, 8-SOCH.sub.3                                  CF.sub.3      C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                                                          7-F, 8-CH.sub.3                                    CF.sub.3      thienylSO.sub.2 NH.sub.2                                                                   7-F, 9OCH.sub.3                                    CF.sub.3      C.sub.6 H.sub.5 F                                                                          8-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 Cl                                                                         8-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 OCH.sub.3                                                                  8-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 CH.sub.3                                                                   8-SO.sub.2 NH.sub.2                                CF.sub.3      C.sub.6 H.sub.5 SOCH.sub.3                                                                 8-SO.sub.2 NH.sub.2                                ______________________________________                                    

                  TABLE XVI                                                       ______________________________________                                        General Structure Ip                                                          B                   R.sup.2                                                   ______________________________________                                         ##STR289##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR290##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR291##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR292##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR293##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR294##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR295##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR296##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR297##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR298##         C.sub.6 H.sub.5 SO.sub.2 CH.sub.3                          ##STR299##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR300##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR301##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR302##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR303##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR304##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR305##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR306##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR307##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                          ##STR308##         C.sub.6 H.sub.5 SO.sub.2 NH.sub.2                         ______________________________________                                    

Within Formula I there is a subclass of compounds of high interestrepresented by Formula II: ##STR309##

wherein A is --(CH₂)_(m) --X--(CH₂)_(n) --;

wherein X is S(O)_(p) or O;

wherein m is 0 or 1;

wherein n is 0 or 1;

wherein p is 0 or 1;

wherein B is selected from aryl and heteroaryl;

wherein R¹ is selected from haloalkyl, aminocarbonyl, alkoxycarbonyl andcyano;

wherein R⁴ is one or more radicals selected from hydrido, halo, alkyland alkoxy; and

wherein R⁵ is selected from alkyl and amino;

or a pharmaceutically-acceptable salt thereof.

A preferred class of compounds consists of those compounds of Formula IIwherein A is --(CH₂)_(m) --X--(CH₂)_(n) --; wherein X is S(O)_(p) or O;wherein m is 0 or 1; wherein n is 0 or 1; wherein p is 0 or 1; wherein Bis selected from phenyl and five membered heteroaryl; wherein R¹ isselected from lower haloalkyl, aminocarbonyl, lower alkoxycarbonyl andcyano; wherein R⁴ is one or more radicals selected from hydrido, halo,lower alkyl and lower alkoxy; and wherein R⁵ is selected from loweralkyl and amino; or a pharmaceutically-acceptable salt thereof.

A class of compounds of particular interest consists of those compoundsof Formula II wherein A is --(CH₂)_(m) --X--(CH₂)_(n) --; wherein X isS(O)_(p) or O; wherein m is 0 or 1; wherein n is 0 or 1; wherein p is 0or 1; wherein B is selected from phenyl, thienyl, furyl and pyrrolyl;wherein R¹ is selected from fluoromethyl, difluoromethyl,trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl,pentafluoroethyl, heptafluoropropyl, difluorochloromethyl,dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl,dichloropropyl, aminocarbonyl, methoxycarbonyl, ethoxycarbonyl,propoxycarbonyl, butoxycarbonyl and cyano; wherein R⁴ is one or moreradicals selected from hydrido, fluoro, chloro, bromo, methyl, ethyl,isopropyl, tert-butyl, isobutyl, hexyl, methoxy, methylenedioxy, ethoxy,propoxy, n-butoxy and tert-butoxy; and wherein R⁵ is selected frommethyl and amino; or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula IIconsists of compounds and pharmaceutically-acceptable salts thereof asfollows:

4-[7-chloro-1,5-dihydro-3-trifluoromethylthieno[3',2':4,5]thiopyrano-s-oxide[3,2-c]pyrazol-1-yl]benzenesulfonamide;

methyl [1-(4-aminosulfonylphenyl)-1,5-dihydro-7-fluoro-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-3-yl]carboxylate;

[1-(4-aminosulfonylphenyl)-1,5-dihydro-7-fluoro-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-3-yl]carboxamide;

4-[1,5-dihydro -6-fluoro-7-methoxy-3-(difluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;

4-[1,5-dihydro-7-fluoro-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;

4-[1,5-dihydro-6-fluoro-7-methoxy-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;

1,5-dihydro-6-fluoro-7-methoxy-1-[4-(methylsulfonyl)phenyl]-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazole;

4-[1,4-dihydro-3-(trifluoromethyl)-[1]benzopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;

methyl[1-[4-(aminosulfonyl)phenyl]-1,4-dihydro-[1]benzopyrano[4,3-c]pyrazol-3-yl]carboxylate;

4-[1,4-dihydro-6-fluoro-3-(trifluoromethyl)-[1]benzopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;

4-[3-(trifluoromethyl)-1H-benzofuro[3,2-c]pyrazol-1-yl]benzenesulfonamide;

4-[1,4-dihydro-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;

methyl[1-[4-(aminosulfonyl)phenyl]-1,4-dihydro-[1]benzothiopyrano[4,3-c]pyrazol-3-carboxylate;

4-[6,7-dichloro-1,4-dihydro-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;

4-[1,4-dihydro-7-fluoro-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;

4-[1,4-dihydro-6-isopropyl-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;

4-[1,4-dihydro-7,8-dimethoxy-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;

4-[1,4-dihydro-7-methoxy-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;

4-[1,4-dihydro-7-methyl-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;

4-[7-chloro-1,4-dihydro-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;

4-[1,5-dihydro-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;

4-[1,5-dihydro-7-methyl-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;

1,5-dihydro-1-[4-(methylsulfonyl)phenyl]-7-methyl-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazole;

4-[7-chloro-1,5-dihydro-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;

4-[1,5-dihydro-7-methoxy-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;

4-[7-chloro-1,5-dihydro-3-trifluoromethyl-[2]thienothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;and

4-[3-cyano-1,4-dihydro[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide.

The term "hydrido" denotes a single hydrogen atom (H). This hydridoradical may be attached, for example, to an oxygen atom to form ahydroxyl radical or two hydrido radicals may be attached to a carbonatom to form a methylene (--CH₂ --) radical. Where used, either alone orwithin other terms such as "haloalkyl", "alkylsulfonyl", "alkoxyalkyl"and "hydroxyalkyl", the term "alkyl" embraces linear or branchedradicals having one to about twenty carbon atoms or, preferably, one toabout twelve carbon atoms. More preferred alkyl radicals are "loweralkyl" radicals having one to about ten carbon atoms. Most preferred arelower alkyl radicals having one to about six carbon atoms. Examples ofsuch radicals include methyl, ethyl, n-propyl, isopropyl, n-butyl,isobutyl, sec-butyl, tert-butyl, pentyl, iso-amyl, hexyl and the like.The term "halo" means halogens such as fluorine, chlorine, bromine oriodine. The term "haloalkyl" embraces radicals wherein any one or moreof the alkyl carbon atoms is substituted with halo as defined above.Specifically embraced are monohaloalkyl, dihaloalkyl and polyhaloalkylradicals. A monohaloalkyl radical, for one example, may have either aniodo, bromo, chloro or fluoro atom within the radical. Dihalo andpolyhaloalkyl radicals may have two or more of the same halo atoms or acombination of different halo radicals. "Lower haloalkyl" embracesradicals having 1-6 carbon atoms. Examples of haloalkyl radicals includefluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl,dichloromethyl, trichloromethyl, trichloromethyl, pentafluoroethyl,heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl,difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl. Theterm "hydroxyalkyl" embraces linear or branched alkyl radicals havingone to about ten carbon atoms any one of which may be substituted withone or more hydroxyl radicals. More preferred hydroxyalkyl radicals are"lower hydroxyalkyl" radicals having one to six carbon atoms and one ormore hydroxyl radicals. Examples of such radicals include hydroxymethyl,hydroxyethyl, hydroxypropyl, hydroxybutyl and hydroxyhexyl. The terms"alkoxy" and "alkoxyalkyl" embrace linear or branched oxy-containingradicals each having alkyl portions of one to about ten carbon atoms.More preferred alkoxy radicals are "lower alkoxy" radicals having one tosix carbon atoms. Examples of such radicals include methoxy, ethoxy,propoxy, butoxy and tert-butoxy. The term "alkoxyalkyl" also embracesalkyl radicals having two or more alkoxy radicals attached to the alkylradical, that is, to form monoalkoxyalkyl and dialkoxyalkyl radicals.More preferred alkoxyalkyl radicals are "lower alkoxyalkyl" radicalshaving one to six carbon atoms and one or two alkoxy radicals. Examplesof such radicals include methoxymethyl, methoxyethyl, ethoxyethyl,methoxybutyl and methoxypropyl. The "alkoxy" or "alkoxyalkyl" radicalsmay be further substituted with one or more halo atoms, such as fluoro,chloro or bromo, to provide "haloalkoxy" or haloalkoxyalkyl radicals.More preferred haloalkoxy radicals are "lower haloalkoxy" radicalshaving one to six carbon atoms and one or more halo radicals. Examplesof such radicals include fluoromethoxy, chloromethoxy, trifluoromethoxy,trifluoroethoxy, fluoroethoxy and fluoropropoxy. The term "aryl", aloneor in combination, means a carbocyclic aromatic system containing one,two or three rings wherein such rings may be attached together in apendent manner or may be fused. The term "aryl" embraces aromaticradicals such as phenyl, naphthyl, tetrahydronaphthyl, indane andbiphenyl. The term "heterocyclic" embraces saturated, partiallysaturated and unsaturated heteroatom-containing ring-shaped radicals,where the heteroatoms may be selected from nitrogen, sulfur and oxygen.Such heterocyclic radicals preferrably include ring systems having 3 to10 members. Examples of saturated heterocyclic radicals includesaturated 3 to 6-membered heteromonocylic group containing 1 to 4nitrogen atoms [e.g. pyrrolidinyl, imidazolidinyl, piperidino,piperazinyl, etc.]; saturated 3 to 6-membered heteromonocyclic groupcontaining 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [e.g.morpholinyl, etc.]; saturated 3 to 6-membered heteromonocyclic groupcontaining 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms [e.g.,thiazolidinyl, etc.]. Examples of partially saturated heterocyclicradicals include dihydrothiophene, dihydropyran, dihydrofuran anddihydrothiazole. The term "heteroaryl" embraces unsaturated heterocyclicradicals. Examples of unsaturated heterocyclic radicals, also termed"heteroaryl" radicals include unsaturated 3 to 6 memberedheteromonocyclic group containing 1 to 4 nitrogen atoms, for example,pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, pyrimidinyl,pyrazinyl, pyridazinyl, triazolyl [e.g., 4H-1,2,4-triazolyl,1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc.]tetrazolyl [e.g.1H-tetrazolyl, 2H-tetrazolyl, etc.], etc.; unsaturated condensedheterocyclic group containing 1 to 5 nitrogen atoms, for example,indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl,indazolyl, benzotriazolyl, tetrazolopyridazinyl [e.g.,tetrazolo[1,5-b]pyridazinyl, etc.], etc.; unsaturated 3 to 6-memberedheteromonocyclic group containing an oxygen atom, for example, pyranyl,furyl, etc.; unsaturated 3 to 6-membered heteromonocyclic groupcontaining a sulfur atom, for example, thienyl, etc.; unsaturated 3- to6-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1to 3 nitrogen atoms, for example, oxazolyl, isoxazolyl, oxadiazolyl[e.g., 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl,etc.]etc.; unsaturated condensed heterocyclic group containing 1 to 2oxygen atoms and 1 to 3 nitrogen atoms [e.g. benzoxazolyl,benzoxadiazolyl, etc.]; unsaturated 3 to 6-membered heteromonocyclicgroup containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, forexample, thiazolyl, thiadiazolyl [e.g., 1,2,4-thiadiazolyl,1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, etc.]and isothiazolyl;unsaturated condensed heterocyclic group containing 1 to 2 sulfur atomsand 1 to 3 nitrogen atoms [e.g., benzothiazolyl, benzothiadiazolyl,etc.]and the like. The term also embraces radicals where heterocyclicradicals are fused with aryl radicals. Examples of such fused bicyclicradicals include benzofuryl, benzothienyl, and the like. Said"heterocyclic" radicals may have 1 to 3 substituents such as loweralkyl, hydroxy, oxo, amino and lower alkylamino. More preferredheteroaryl radicals include five to six membered heteroaryl radicals.The term "alkylthio" embraces radicals containing a linear or branchedalkyl radical, of one to about ten carbon atoms attached to a divalentsulfur atom. More preferred alkylthio radicals are "lower alkylthio"radicals having alkyl radicals of one to six carbon atoms. Examples ofsuch lower alkylthio radicals are methylthio, ethylthio, propylthio,butylthio and hexylthio. The term "alkylthioalkyl" embraces alkylthioradicals attached to an alkyl radical. More preferred alkylthioalkylradicals are "lower alkylthioalkyl" radicals having alkyl radicals ofone to six carbon atoms and an alkylthio radical as described above.Examples of such radicals include methylthiomethyl. The term "arylthio"embraces radicals containing an aryl radical, attached to a divalentsulfur atom, such as a phenylthio radical. The term "alkylsulfinyl"embraces radicals containing a linear or branched alkyl radical, of oneto ten carbon atoms, attached to a divalent --S(═O)-radical. Morepreferred alkylsulfinyl radicals are "lower alkylsulfinyl" radicalshaving one to six carbon atoms. Examples of such lower alkylsulfinylradicals include methylsulfinyl, ethylsulfinyl, butylsulfinyl andhexylsulfinyl. The term "alkylsulfinylalkyl" embraces alkylsulfinylradicals attached to an alkyl radical, where alkyl and alkylsulfinyl aredefined as above. More preferred alkylsulfinylalkyl radicals are "loweralkylsulfinylalkyl" radicals having one to six carbon atoms. Examples ofsuch lower alkylsulfinylalkyl radicals include methylsulfinylmethyl. Theterm "sulfonyl", whether used alone or linked to other terms such asalkylsulfonyl, denotes respectively divalent radicals --SO₂ --."Alkylsulfonyl" embraces alkyl radicals attached to a sulfonyl radical,where alkyl is defined as above. More preferred alkylsulfonyl radicalsare "lower alkylsulfonyl" radicals having one to six carbon atoms.Examples of such lower alkylsulfonyl radicals include methylsulfonyl,ethylsulfonyl and propylsulfonyl. The term "alkylsulfonylalkyl" embracesalkylsulfonyl radicals attached to an alkyl radical, where alkyl andalkylsulfonyl are defined as above. More preferred alkylsulfonylalkylradicals are "lower alkylsulfonylalkyl" radicals having one to sixcarbon atoms. Examples of such lower alkylsulfonylalkyl radicals includemethylsulfonylmethyl, ethylsulfonylmethyl and propylsulfonylmethyl. Theterm "arylsulfonyl" embraces aryl radicals as defined above, attached toa sulfonyl radical. Examples of such radicals include phenylsulfonyl.The terms "sulfamyl", "aminosulfonyl" and "sulfonamidyl" denotes NH₂ O₂S--. The terms "N-alkylsulfamyl" and "N,N-dialkylsulfamyl" denotesulfamyl radicals substituted, respectively, with one alkyl radical, acycloalkyl ring, or two alkyl radicals. The terms "N-arylsulfamyl" and"N-alkyl-N-arylsulfamyl" denote sulfamyl radicals substituted with onearyl radical or one alkyl and one aryl radical, respectively. The term"acyl" denotes a radical provided by the residue after removal ofhydroxyl from an organic acid. Examples of such acyl radicals includeformyl, alkanoyl and aroyl radicals. The terms "carboxy" or "carboxyl",whether used alone or with other terms, such as "carboxyalkyl", denotes--CO₂ H. The term "carbonyl", whether used alone or with other terms,such as "alkoxycarbonyl", denotes --(C═O)--. The term "alkoxycarbonyl"means a radical containing an alkoxy radical, as defined above, attachedvia an oxygen atom to a carbonyl radical. Preferably, "loweralkoxycarbonyl" embraces alkoxy radicals having one to six carbon atoms.Examples of such "lower alkoxycarbonyl" ester radicals includesubstituted or unsubstituted methoxycarbonyl, ethoxycarbonyl,propoxycarbonyl, butoxycarbonyl and hexyloxycarbonyl. The term"alkylcarbonyl" includes radicals having alkyl, aryl and aralkylradicals, respectively, as defined above, attached via an oxygen atom toa carbonyl radical. More preferred alkylcarbonyl radicals are "loweralkylcarbonyl" radicals having one to six carbon atoms. Examples of suchradicals include methylcarbonyl and ethylcarbonyl. The term"alkylcarbonylalkyl" embraces radicals having "alkylcarbonyl", asdefined above substituted to an alkyl radical. More preferredalkylcarbonylalkyl radicals are "lower alkylcarbonylalkyl" having loweralkylcarbonyl radicals as defined above attached to one to six carbonatoms. Examples of such lower alkylcarbonylalkyl radicals includemethylcarbonylmethyl. The term "alkoxycarbonylalkyl" embraces radicalshaving "alkoxycarbonyl", as defined above substituted to an alkylradical. More preferred alkoxycarbonylalkyl radicals are "loweralkoxycarbonylalkyl" having lower alkoxycarbonyl radicals as definedabove attached to one to six carbon atoms. Examples of such loweralkoxycarbonylalkyl radicals include methoxycarbonylmethyl. The terms"alkanoyl" or "carboxyalkyl" embrace radicals having a carboxy radicalas defined above, attached to an alkyl radical. The alkanoyl radicalsmay be substituted or unsubstituted, such as formyl, acetyl, propionyl,butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl,trifluoroacetyl or the like, in which the preferable one is formyl,acetyl, propionyl or trifluoroacetyl. The term "aminoalkyl" embracesalkyl radicals substituted with amino radicals. More preferredaminoalkyl radicals are "lower aminoalkyl" having one to six carbonatoms. Examples include aminomethyl, aminoethyl and aminobutyl. The term"alkylamino" denotes amino groups which have been substituted with oneor two alkyl radicals. Suitable "alkylamino" may be mono or dialkylaminosuch as N-methylamino, N-ethylamino, N,N-dimethylamino, N,N-diethylaminoor the like. The term "alkylaminocarbonyl" embraces alkylamino radicals,as described above, attached to a carbonyl radical. More preferredalkylaminocarbonyl radicals are "lower alkylaminocarbonyl" having loweralkylamino radicals, as described above, attached to a carbonyl radical.Examples of such radicals include N-methylaminocarbonyl andN,N-dimethylcarbonyl. The term "arylamino" denotes amino groups whichhave been substituted with one or two aryl radicals, such asN-phenylamino. The "arylamino" radicals may be further substituted onthe aryl ring portion of the radical. The term "arylaminocarbonyl"embraces arylamino radicals, as described above, connected to a carbonylradical. An example of such radicals includes phenylaminocarbonyl. Theterm "N-alkyl-N-arylaminocarbonyl" embraces arylamino radicals, asdescribed above, to a carbonyl radical. An example of such radicalsincludes phenylaminocarbonyl. The term "aminocarbonyl" denotes an amidegroup of the formula --C(═O)NH₂. The term "N-alkyl-N-arylaminocarbonyl"embraces aminocarbonyl radicals, as described above, substituted withone alkyl and one aryl radical. An example of such radicals isN-methyl-N-phenylaminocarbonyl. The term "aminocarbonylalkyl" denotes anaminocarbonyl radical attached to an alkyl radical, as described above.An example of such radicals is aminocarbonylmethyl. The term "amidino"denotes an --C(═NH)--NH₂ radical. The term "cyanoamidino" denotes an--C(═N--CN)--NH₂ radical. The term "cycloalkyl" embraces radicals havingthree to ten carbon atoms, such as cyclopropyl cyclobutyl, cyclopentyl,cyclohexyl and cycloheptyl. The term "acyl", whether used alone, orwithin a term such as "acylamino", denotes a radical provided by theresidue after removal of hydroxyl from an organic acid. The term"acylamino" embraces an amino radical substituted with an acyl group. Anexamples of an "acylamino" radical is acetylamino (CH₃ C(═O)--NH--).

The present invention comprises a pharmaceutical composition comprisinga therapeutically-effective amount of a compound of Formula I inassociation with at least one pharmaceutically-acceptable carrier,adjuvant or diluent.

The present invention also comprises a method of treating inflammationor inflammation-associated disorders in a subject, the method comprisingadministering to the subject having such inflammation or disorder atherapeutically-effective amount of a compound of Formula I.

Also included in the family of compounds of Formula I are thepharmaceutically-acceptable salts thereof. The term"pharmaceutically-acceptable salts" embraces salts commonly used to formalkali metal salts and to form addition salts of free acids or freebases. The nature of the salt is not critical, provided that it ispharmaceutically-acceptable. Suitable pharmaceutically-acceptable acidaddition salts of compounds of Formula I may be prepared from aninorganic acid or from an organic acid. Examples of such inorganic acidsare hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuricand phosphoric acid. Appropriate organic acids may be selected fromaliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic,carboxylic and sulfonic classes of organic acids, example of which areformic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic,tartaric, citric, ascorbic, glucuronic, maleic, fumaric, pyruvic,aspartic, glutamic, benzoic, anthranilic, mesylic, salicyclic,salicyclic, p-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic),methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic,toluenesulfonic, 2-hydroxyethanesulfonic, sulfanilic, stearic,cyclohexylaminosulfonic, algenic, β-hydroxybutyric, salicyclic,galactaric and galacturonic acid. Suitable pharmaceutically-acceptablebase addition salts of compounds of Formula I include metallic saltsmade from aluminum, calcium, lithium, magnesium, potassium, sodium andzinc or organic salts made from N,N'-dibenzylethylenediamine,chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine(N-methylglucamine) and procaine. All of these salts may be prepared byconventional means from the corresponding compound of Formula I byreacting, for example, the appropriate acid or base with the compound ofFormula I.

GENERAL SYNTHETIC PROCEDURES

The compounds of the invention can be synthesized according to thefollowing procedures of Schemes I-XII, wherein the R¹ -R⁵ substituentsare as defined for Formulas I-II, above, except where further noted.##STR310##

Synthetic Scheme I illustrates the procedure used to prepare theantiinflammatory pyrazoles 3 of the present invention. 1,3-Dicarbonylcompounds such as 1, or the shown enol form which is in equilibrium tothe diketone, are reacted with a hydrazine hydrochloride 2 in warmethanol to provide the pyrazoles 3 via a condensation reaction.##STR311##

Synthetic Scheme II illustrates the four step procedure for thepreparation of substituted diketones 8. In step one, an appropriatelysubstituted methyl halide 4 (where X is chloro for example) is convertedinto the corresponding thiouronium salt 5 upon treatment with thiourea.In step two, the thiouronium salt 5 is converted according to theprocedure of Lumma and Berchtold (J. Org. Chem., 34, 1566 (1969)) to thefree mercaptide and then trapped with chloroacetic acid or a relatedsalt to provide the acetic acid derivatives 6. In step three, the acids6 are reacted with trifluoroacetic anhydride (TFAA) in trifluoroaceticacid (TFA) to give the ketones 7. In step four, the ketones 7 are firsttreated with base, such as sodium methoxide or lithium diisopropylamide(LDA), followed by condensation with a suitable acylating agent, R¹COLG, (where LG represents an appropriate leaving group such as methoxy,chloro, imidazole and the like) in an appropriate solvent, such asmethanol, diethyl ether or tetrahydrofuran, to provide the desireddiketones 8 which are suitable for conversion into antiinflammatorypyrazoles as illustrated in Scheme I. ##STR312##

Synthetic Scheme III illustrates the four step procedure for thepreparation of substituted isothiochromanone 1,3-carbonyl derivatives13. In step one, an appropriately substituted benzyl alcohol 9 isconverted into the corresponding benzyl chloride by stirring withconcentrated hydrochloric acid and then immediately converted into athiouronium salt 10 upon treatment with thiourea at reflux. In step two,the thiouronium salt is converted to the free mercaptide and thentrapped with chloroacetic acid or a related salt to provide the aceticacid derivatives 11. In step three, the acids 11 are reacted withtrifluoroacetic anhydride (TFAA) in trifluoroacetic acid (TFA) to givethe isothiochromanone products 12. In step four, the isothiochromanones12 are first treated with base, such as sodium methoxide, sodiumbistrimethylsilylamide or lithium diisopropylamide (LDA), followed bycondensation with a suitable acylating agent, R¹ COLG, (where LG isdefined as in Scheme II) in an appropriate solvent, such as methanol,diethyl ether or tetrahydrofuran, to provide 1,3-dicarbonyl compounds 13which are suitable for conversion into antiinflammatory pyrazoles asillustrated in Scheme I.

Alternatively, the dicarbonyl compounds 13 can be directly prepared fromcommercially available isothiochromanones 12. The thiouronium salts 10can be prepared from commercially available benzyl halides. ##STR313##

Synthetic Scheme IV illustrates a three step procedure used for thepreparation of substituted thiochromanone 1,3-dicarbonyl derivatives 17.In step one, an appropriate substituted thiophenol 14 is converted intothe corresponding propionic acid derivatives 15 upon treatment withacrylic acid at a temperature in a range of room temperature to about50° C. In step two, the propionic acids 15 are subjected to treatmentwith a mixture of trifluoroacetic anhydride and trifluoroacetic acid toeffect intramolecular Friedel-Crafts acylation, thus providingthiochromanones 16. In the last step, substituted thiochromanones 16 arefirst treated with a base, such as lithium diisopropyl amide or sodiummethoxide (LDA), followed by condensation with suitable acylating agentsR¹ COLG (as defined in Scheme II) in an appropriate solvent such asdiethylether, methanol or tetrahydrofuran to provide the 1,3-dicarbonylcompounds 17 which are suitable for conversion into antiinflammatorypyrazoles as illustrated in Scheme I.

Alternatively, the dicarbonyl compounds 17 can be directly prepared fromcommercially available thio-4-chromanones 16. ##STR314##

Synthetic Scheme V details the three step procedure used to preparesubstituted 1,3-dicarbonyl chromanone derivatives 21. In step one,substituted phenols 18 are condensed with acrylic acid to afford3-phenoxypropionic acids 19. In step two, the acids 19 are treated witha mixture of trifluoroacetic anhydride and trifluoroacetic acid toaffect intramolecular Friedel-Crafts acylation affording selectedchromanones 20. In step three, substituted chromanones 20 are firsttreated with base, such as lithiumdiisopropylamide (LDA) or sodiummethoxide followed by condensation with suitable acylating agents, R¹CO-LG (where LG represents leaving group as previously defined in SchemeII in an appropriate solvent such as diethyl ether or methanol) toprovide 1,3-dicarbonyl compounds 21 which are suitable for conversioninto antiinflammatory pyrazoles as illustrated in Scheme I.

Alternatively, the dicarbonyl compounds 21 can be directly formed fromcommercially available chromanones 20. ##STR315##

Synthetic Scheme VI illustrates a three step procedure used to preparesubstituted 1,3-dicarbonyl isochromanone derivatives 25. In step one,selected benzyl alcohol derivatives 22 are treated with sodium hydrideand subsequently treated with ethyl bromoacetate to provide the desiredethers 23. In step two, the ester group of 23 is hydrolyzed with aqueoussodium hydroxide and then treated with a mixture of trifluoroacetic acidand trifluoroacetic anhydride to promote intramolecular Friedel-Craftsacylation affording isochromanone 24 derivatives. In the third step, theisochromanones 24 are first treated with a base such as lithiumdiisopropylamide (LDA) or sodium methoxide followed by condensation withsuitable acylating agents (R¹ COLG) to provide the 1,3-dicarbonylcompounds 25 which were suitable for conversion into antiinflammatorypyrazoles as illustrated in Scheme I. ##STR316##

Synthetic Scheme VII illustrates a procedure used to prepare themethylsulfonylphenylhydrazine hydrochloride and thesulfonamidylphenylhydrazine hydrochlorides 27 as used in Scheme I. Thesulfonylphenylhydrazine 26 is converted to the hydrochloride salt bystirring with a 4N solution of hydrochloric acid in a solvent such asdioxane. ##STR317##

Synthetic Scheme VIII illustrates a procedure used to preparesubstituted 3-coumaranones 29. Coumaranones 28 are first treated with abase, such as lithium diisopropyl amide or sodium methoxide (LDA)followed by condensation with suitable acylating agents R¹ COLG (asdefined in Scheme II) in an appropriate solvent such as diethylether,methanol or tetrahydrofuran to provide the 1,3-dicarbonyl compounds 29which are suitable for conversion into antiinflammatory pyrazoles asillustrated in Scheme I. ##STR318##

Synthetic Scheme IX illustrates a two step procedure used for thepreparation of substituted benzylalcohols 9. In step one, a mixture ofpotassium tert-butoxide and anhydrous tetrahydrofuran, cooled to -78° C.and treated with a 1.6M solution of n-butyllithium in hexanes, is addedto an appropriate substituted benzene 30 to yield the benzoic acid 31.In step two, the benzoic acid 31 is dissolved in a solvent, such astetrahydrofuran, and treated with a reducing agent, such as boranedimethyl sulfide complex, to form the desired benzyl alcohol 9.##STR319##

Synthetic Scheme X illustrates a procedure used for the preparation ofthe antiinflammatory oxidized thio-containing fused tricyclic pyrazoles33. The appropriate pyrazole 32 from Scheme I, where A is S or--(CH₂)_(m) S(CH₂)_(n) --, is treated with an oxidizing agent such asm-chloroperbenzoic acid (MCPBA) or hydrogen peroxide. Compounds havingdiffering amounts of oxidation (sulfinyls and sulfones) can beseparated, such as by chromatography. ##STR320##

Synthetic Scheme XI shows procedures for preparing antiinflammatoryagents 36, 37 and 38 of Formula I. The esters 35, which can be preparedas shown in Scheme I, is dissolved in aqueous ethanol and a base such as10% NaOH is added. The reaction is heated to reflux to give the acids36. The acids 36 can be converted to the fused pyrazole with a hydridoradical by decarboxylation by heating to about 290° C. to give thedecarboxylated products 37. The acids 36 also can be converted to theappropriate amides 38 by dissolving in methanol and treating with anappropriate amine in the presence of a condensing agent such asdicyclohexylcarbodiimide (DCC). The amides 38 can also be prepared bydirect aminolysis of 35. ##STR321##

Synthetic Scheme XII shows the two step procedure for preparation ofsubstituted heteroarylhydrazine compounds 41 as used in Scheme I whereR² is thienyl. In step 1, the heteroarylsulfonyl chloride 39 (where LGrepresents a leaving group such as halo) is treated with ammonia to givethe heteroaryl sulfonamides 40. In step 2, the heteroaryl sulfonamides40 are treated with hydrazine to give the substitutedheteroarylhydrazines 41.

The following examples contain detailed descriptions of the methods ofpreparation of compounds of Formula I-II. These detailed descriptionsfall within the scope, and serve to exemplify, the above describedGeneral Synthetic Procedures which form part of the invention. Thesedetailed descriptions are presented for illustrative purposes only andare not intended as a restriction on the scope of the invention. Allparts are by weight and temperatures are in Degrees centigrade unlessotherwise indicated. ##STR322##4-[1,5-Dihydro-6-fluoro-7-methoxy-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of 2-fluoro-3-methoxybenzoic acid

A mixture of potassium tert-butoxide (30.80 g, 274 mmol) and anhydroustetrahydrofuran (300 mL) was cooled to -78° C. and treated with a 1.6Msolution of n-butyllithium (172 mL, 275 mmol) in hexanes. After stirringfor 15 minutes, 2-fluoroanisole (31.35 g, 248 mmol) was added and thereaction was stirred an additional 1.8 hours. The reaction was pouredinto a 2 L Erlenmeyer flask containing dry ice and warmed to roomtemperature. Water (250 mL) was added and after extracting with ether(160 mL), the aqueous layer was acidified with concentrated hydrochloricacid, and filtered to give 2-fluoro-3-methoxybenzoic acid (21.43 g, 51%)as a yellow solid: mp 155°-160° C.; ¹ H NMR (acetone-d₆) 300 MHz 7.46(ddd, J=6.0 Hz J=1.8 Hz J=1.4 Hz, 1H) 7.36 (dt, J=1.6 Hz J=8.1 Hz, 1H)7.20 (dt, J=1.4 Hz J=8.1 Hz, 1H) 3.92 (s, 3H); ¹⁹ F NMR (acetone-d₆) 300MHz -134.04 (m). Mass spectrum: M+H=171.

Step 2

Preparation of 2-fluoro-3-methoxybenzyl alcohol

2-Fluoro-3-methoxybenzoic acid from Step 1 (16.65 g, 98 mmol) wasdissolved in anhydrous tetrahydrofuran (60 mL), cooled in an ice bath,and treated with borane dimethyl sulfide complex (19 mL, 190 mmol). Thereaction was stirred at room temperature for 4.2 hours, quenched by theslow addition of methanol, and concentrated in vacuo. The residue wasdissolved in ethyl acetate, treated with 3N hydrochloric acid andfiltered through diatomaceous earth. The organic layer of the filtratewas collected, washed with NaHCO₃, brine, dried over MgSO₄ andreconcentrated in vacuo to give 2-fluoro-3-methoxybenzyl alcohol (12.35g, 81%) as a white solid: mp 53°-57° C.; ¹ H NMR (acetone-d₆) 300 MHz7.07 (m, 3H) 4.67 (d, J=5.8 Hz, 2H) 4.24 (t, J=5.8 Hz, 1H) 3.86 (s, 3H);¹⁹ F NMR (acetone-d₆) 300 MHz -144.77 (m).

Step 3

Preparation of 2-fluoro-3-methoxybenzyl chloride

2-Fluoro-3-methoxybenzyl alcohol from Step 2 (12.16 g, 78 mmol) wasdissolved in concentrated hydrochloric acid (60 mL) and hydrochloricacid gas was bubbled through the solution for 3 minutes. The flask wascapped and the reaction stirred at room temperature (21 hours). Thereaction mixture was extracted with ether, dried over MgSO₄ andconcentrated in vacuo to give 2-fluoro-3-methoxybenzyl chloride (10.36g, 76%) as a green oil: ¹ H NMR (acetone-d₆) 300 MHz 7.12 (m, 2H) 7.05(m, 1H) 4.73 (s, 2H) 3.89 (s, 3H); ¹⁹ F NMR (acetone-d₆) 300 MHz-142.07(m).

Step 4

Preparation of S-(2-fluoro-3-methoxybenzyl)-isothiouronium chloride

Thiourea (4.47 g, 59 mmol) was added to a solution of2-fluoro-3-methoxybenzyl chloride from Step 3 (10.20 g, 58 mmol) inmethanol (25 mL). The reaction was heated to reflux for 3.3 hours,concentrated in vacuo, triturated with ether, and filtered to give awhite solid (14.65 g, 100%).

Step 5

Preparation of 3-(2-fluoro-3-methoxyphenylthio)propanoic acid

A 500 mL flask was charged with the thiouronium salt from Step 4 (14.65g, 58 mmol), sodium chloroacetate (10.44 g, 90 mmol), ethanol (60 mL)and water (25 mL). After heating to reflux, a solution of NaOH (10.66 g,266 mmol) in water (35 mL) was added to the reaction dropwise. Afterstirring for 16.6 hours, the reaction was acidified with concentratedhydrochloric acid, extracted with ether, washed with brine, dried overMgSO₄, concentrated in vacuo and recrystallized from ether/hexane togive a brown solid (7.70 g, 57%): mp 72°-74° C.; ¹ H NMR (CDCl₃) 300 MHz7.03 (m, 1H) 6.91 (m, 2H) 3.89 (d, J=1.0 Hz, 2H) 3.88 (s, 3H) 3.19 (s,2H); ¹⁹ F NMR (CDCl₃) 300 MHz -140.76 (m).

Step 6

Preparation of 8-fluoro-7-methoxyisothiochroman-4-one

The acid from Step 5 (7.63 g, 33 mmol) was dissolved in trifluoroaceticacid (12 mL), treated with trifluoroacetic anhydride (4 mL) and stirredat room temperature (8 minutes). The reaction was poured into 10% Na₂CO₃ (50 mL) and extracted with ethyl acetate, washed with brine, driedover MgSO₄ and concentrated in vacuo to give8-fluoro-7-methoxyisothiochroman-4-one (5.42 g, 77%) as a brown solid:mp 85°-92° C.; ¹ H NMR (CDCl₃) 300 MHz 7.83 (d, J=8.9 Hz, 1H) 7.19 (t,J=8.5 Hz, 1H) 4.01 (s, 2H) 3.98 (s, 3H) 3.55 (s, 2H); ¹⁹ F NMR (CDCl₃)300 MHz -141.24 (m).

Step 7

Preparation of6-fluoro-7-methoxy-3-(trifluoroacetyl)isothiochroman-4-one

8-Fluoro-7-methoxyisothiochroman-4-one from Step 6 (1.70 g, 8.0 mmol)was dissolved in anhydrous tetrahydrofuran (30 mL), cooled to -78° C.,and treated with a 1.0M tetrahydrofuran solution of sodiumbistrimethylsilyl amide (10 mL, 10 mmol). After 30 minutes,N-trifluoroacetylimidazole (1.85 g in 10.0 mL THF, 11.3 mmol) was addedand the reaction was stirred and warmed to room temperature overnight(19.4 hours). The reaction was treated with 1N hydrochloric acid (30mL). The organic layer was collected, washed with brine, dried overMgSO₄, concentrated in vacuo and recrystallized fromdichloromethane/isooctane to give the diketone (1.14 g, 46%) as a brownsolid: mp 162°-164° C.; ¹ H NMR (CDCl₃) 300 MHz 15.50 (s, 1H) 7.82 (dd,J=8.9 Hz J=1.0 Hz, 1H) 6.99 (t, J=8.5 Hz, 1H) 3.99 (s, 3H) 3.89 (s, 2H)2.43 (s, 2H); ¹⁹ F NMR (CDCl₃) 300 MHz: -72.46 (s) -140.30 (d). Massspectrum: M+H=309.

Step 8

Preparation of4-[6-fluoro-1,5-dihydro-7-methoxy-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

4-Sulfonamidophenylhydrazine hydrochloride (0.77 g, 3.4 mmol) was addedto a stirred solution of the diketone from Step 7 (0.93 g, 3.0 mmol) inethanol (10 mL). The reaction was heated to reflux and stirred for 20.4hours. The reaction mixture was filtered while hot to give the pyrazoleas gray needles (0.55 g, 40%): mp 250°-252° C.; ¹ H NMR (acetone-d₆) 300MHz 8.08 (d, J=8.9 Hz, 2H) 7.85 (d, J=8.7 Hz, 2H) 7.01 (t, J=8.7 Hz, 1H)6.81 (br s, 2H) 6.72 (dd, J=8.6 Hz J=1.9 Hz, 1H) 4.20 (s, 2H) 3.91 (s,3H); ¹⁹ F NMR (acetone-d₆) 300 MHz -63.32 (s) -140.16 (d). ##STR323##1,5-Dihydro-6-fluoro-7-methoxy-1-[(4-methylsulfonyl)phenyl]-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazole

4-(Methylsulfonyl)phenylhydrazine (0.75 g, 4.0 mmol) was converted tothe hydrochloride salt by stirring with a 4N solution of hydrochloricacid in dioxane (10 mL) for 30 minutes. The dioxane was removed in vacuoand the 4-(methylsulfonyl)phenyl hydrazine hydrochloride was combinedwith the diketone from Example 1, Step 7 (0.89 g, 2.9 mmol) and ethanol(15 mL), heated to reflux and stirred for 14.5 hours. The reactionmixture was filtered while hot and the filtrate was concentrated invacuo. The residue was dissolved in ethyl acetate, washed with water andwith brine, dried over MgSO₄, reconcentrated in vacuo and passed througha column of silica gel, eluting with 20% ethyl acetate/hexane to givethe pyrazole (0.46 g, 35%) as a yellow solid: mp 213°-215° C.; ¹ H NMR(acetone-d₆) 300 MHz 8.15 (d, J=8.7 Hz, 2H) 7.94 (d, J=8.7 Hz, 2H) 7.01(t, J=8.7 Hz, 1H) 6.73 (d, J=8.7 Hz, 1H) 4.21 (s, 2H) 3.90 (s, 3H) 3.23(s, 3H); ¹⁹ F NMR (acetone-d₆) 300 MHz -63.41 (s) -140.17 (d). Massspectrum: M+=458.1. ##STR324##4-[1,4-Dihydro-3-(trifluoromethyl)-[1]benzopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of 3-(trifluoroacetyl)-4-chromanone

Ethyl trifluoroacetate (9.78 g, 68 mmol) was placed in a 250 mL roundbottom flask, and dissolved in ether (50 mL). To the stirred solutionwas added 25% sodium methoxide (15.11 g, 70 mmol), followed by4-chromanone (10.07 g, 68 mmol) dissolved in ether (25 mL). The reactionwas stirred at room temperature overnight (18.3 hours), poured into aseparatory funnel and washed with 3N hydrochloric acid (20 mL) and withbrine (20 mL), dried over MgSO₄, concentrated in vacuo, andrecrystallized from ether/hexane to give a yellow solid (10.72 g, 65%):mp 81°-83° C.; ¹ H NMR (CDCl₃) 300 MHz 16.04 (br s, 1H) 7.84 (d, J=7.9Hz, 1H) 7.51 (m, 1H) 7.09 (m, 1H) 6.98 (d, J=8.5 Hz, 1H) 5.08 (s, 2H);¹⁹ F NMR (CDCl₃) 300 MHz: -72.56 (s). Mass spectrum: M+=244.

Step 2

Preparation of4-[1,4-dihydro-3-(trifluoromethyl)-[1]benzopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

4-Sulfonamidophenylhydrazine hydrochloride (4.57 g, 20.4 mmol) was addedto a stirred solution of the diketone from Step 1 (4.59 g, 18.8 mmol) inethanol (80 mL). The reaction was heated to reflux and stirred overnight(17.3 hours). The reaction mixture was filtered while hot to give thepyrazole as a white solid (3.99 g, 54%). Upon cooling, the filtrateyielded an additional 1.97 g (26%): mp 250°-251° C.; ¹ H NMR(acetone-d₆) 300 MHz 8.14 (d, J=8.7 Hz, 2H), 7.87 (d, J=8.7 Hz, 2H) 7.30(m, 1H), 7.08 (d, J=8.1Hz, 1H) 6.89 (m, 3H) 5.41 (s, 2H); ¹⁹ F NMR(acetone-d₆) 300 MHz -62.42 (s). High resolution mass spectrum Calc'd.for C₁₇ H₁₂ F₃ N₃ O₃ S: 395.0551. Found: 395.0551. ##STR325##Methyl[1-[4-(aminosulfonyl)phenyl]-1,4-dihydro-[1]benzopyrano[4,3-c]pyrazol-3-yl]carboxylate

Step 1

Preparation of methyl-3-(1-oxo-2-carboxy)-4-chromanone

A 500 mL flask was charged with 4-chromanone (9.72 g, 65.6 mmol),dimethyl oxalate (8.92 g, 75.5 mmol) and methanol (75 mL). The solutionwas treated with sodium methoxide (25%) in methanol (18.52 g, 85.7 mmol)and stirred at room temperature for 18.8 hours. The reaction was treatedwith 3N hydrochloric acid (30 mL), filtered, and recrystallized fromethyl acetate/isooctane to give the diketone (11.31 g, 74%) as a yellowsolid: mp 85°-87° C.; ¹ H NMR (acetone-d₆) 300 MHz 7.87 (d, J=7.9 Hz,1H) 7.61 (m, 1H) 7.14 (m, 1H) 7.02 (d, J=8.3 Hz, 1H) 5.35 (s, 2H) 3.92(s, 3H). Mass spectrum: M+Li=234.

Step 2

Preparation of methyl[1-[4-(aminosulfonyl)phenyl]-1,4-dihydro-[1]benzopyrano[4,3-c]pyrazol-3-yl]carboxylate

4-Sulfonamidophenylhydrazine hydrochloride (6.52 g, 29.1 mmol) was addedto a stirred solution of the diketone from Step 1 (6.23 g, 26.6 mmol) inmethanol (MeOH) (150 mL). The reaction was heated to reflux and stirredfor 15.1 hours. The reaction mixture was filtered, washed with MeOH anddried under vacuum to give the pyrazole as a pale green solid (9.81 g,96%): mp>304° C.; ¹ H NMR (DMSO-d₆) 300 MHz 8.02 (d, J=8.7 Hz, 2H) 7.83(d, J=8.5 Hz, 2H) 7.60 (br s, 2H) 7.25 (2d, 1H) 7.06 (d, J=7.5 Hz,1H)6.84 (2d, 1H) 6.71 (d, J=7.9 Hz, 1H) 5.46 (s, 2H) 3.85 (s, 3H). Massspectrum: M+H=386. ##STR326##4-[1,4-Dihydro-8-fluoro-3-(trifluoromethyl)-[1]benzopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of 6-fluoro-3-(trifluoroacetyl)-4-chromanone

Ethyl trifluoroacetate (4.33 g, 30 mmol) was dissolved in ether (25 mL)and treated with sodium methoxide (25%, 7.08 g, 33 mmol). To the stirredsolution was added 6-fluoro-4-chromanone (4.92 g, 30 mmol) andadditional ether (10 mL). The reaction was stirred at room temperatureovernight (19.0 hours) and treated with 3N hydrochloric acid (15 mL).The organic layer was collected, washed with brine, dried over MgSO₄,concentrated in vacuo and recrystallized from ether/hexane to give ayellow solid (3.98 g, 51%): mp 107°-112° C.; ¹ H NMR (CDCl₃) 300 MHz14.95 (s, 1H) 7.52 (dd, 1H) 7.23 (m, 1H) 6.97 (m, 1H) 5.07 (s, 2H); ¹⁹ FNMR (CDCl₃) 300 MHz -72.60 (s), -119.93 (m). Mass spectrum: M+=262.

Step 2

Preparation of4-[1,4-dihydro-8-fluoro-3-(trifluoromethyl)-[1]benzopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

4-Sulfonamidophenylhydrazine hydrochloride (1.54 g, 6.9 mmol) was addedto a stirred solution of the diketone from Step 1 (1.62 g, 6.2 mmol) inethanol (35 mL). The reaction was heated to reflux and stirred overnight(17.3 hours). The reaction mixture was filtered while hot to give thepyrazole as a white solid (1.09 g, 43%). Upon cooling, the filtrateyielded an additional 0.70 g (27%): mp 251°-251.5° C.; ¹ H NMR(acetone-d₆) 300 MHz 8.17 (d, J=8.5 Hz, 2H) 7.91 (d, J=8.7 Hz, 2H) 7.11(m, 2H) 6.87 (br s, 1H) 6.58 (dd, J=2.4Hz, 9.5Hz, 3H) 5.41 (s, 2H); ¹⁹ FNMR (acetone-d₆) 300 MHz -62.46 (s). High resolution mass spectrumCalc'd. for C₁₇ H₁₁ F₄ N₃ O₃ S: 413.0457. Found: 413.0462. ##STR327##4-[3-(Trifluoromethyl)-1H-benzofuro[3,2-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of 2-(trifluoroacetyl)-3-coumaranone

Ethyl trifluoroacetate (1.90 g, 14 mmol) was dissolved in ether (15 mL)and treated with sodium methoxide (25%) (3.67 g, 17 mmol). To thestirred solution was added 3-coumaranone (1.50 g, 11 mmol). The reactionwas stirred at room temperature overnight (19 hours) and treated with 3NHCl (8 mL). The organic layer was collected, washed with brine, driedover MgSO₄, and concentrated in vacuo to give a reddish brown solid(2.19 g, 85%): mp 108°-111° C.; ¹ H NMR (CDCl₃) 300 MHz 7.84 (d, J=8.1Hz, 1H) 7.66 (m, 1H) 7.52 (d, J=8.7 Hz, 1H) 7.37 (m, 1H). Mass spectrum:M+H=231.

Step 2

Preparation of4-[3-(trifluoromethyl)-1H-benzofuro[3,2-c]pyrazol-1-yl]benzenesulfonamide

4-Sulfonamidophenylhydrazine hydrochloride (1.15 g, 5.0 mmol) was addedto a stirred solution of the diketone from Step 1 (1.13 g, 4.9 mmol) inethanol (10 mL). The reaction was heated to reflux and stirred for 2.5hours. The reaction mixture was filtered to give the pyrazole as a brownsolid (1.07 g, 57%): mp 190°-195° C.; ¹ H NMR (acetone-d₆) 300 MHz7.82-7.90 (m, 3H) 7.34-7.53 (m, 5H); ¹⁹ F NMR (acetone-d₆) 300 MHz-65.47 (s). ##STR328##4-[1,4-Dihydro-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of 3-(trifluoroacetyl)thio-4-chromanone

Ethyl trifluoroacetate (8.78 g, 62 mmol) was placed in a 250 mL roundbottom flask, and dissolved in ether (50 mL). To the stirred solutionwas added sodium methoxide (14.35 g, 66 mmol) followed bythio-4-chromanone (9.43 g, 57 mmol) dissolved in ether (10 mL). Thereaction was stirred at room temperature overnight (17.8 hrs) andtreated with 3N HCl (25 mL). The organic layer was collected, washedwith brine, dried over MgSO₄, concentrated in vacuo and recrystallizedfrom ether/hexane to give a yellow solid (10.20 g, 68%): mp 75°-79° C.;¹ H NMR (CDCl₃) 300 MHz 15.62 (s, 1H) 7.99 (d, J=7.9Hz, 1H) 7.24-7.42(m, 3H) 3.81 (s,2H); ¹⁹ F NMR (CDCl₃) 300 MHz -71.92 (s). Mass spectrum:M+=260.

Step 2

Preparation of4-[1,4-dihydro-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

4-Sulfonamidophenylhydrazine hydrochloride (5.74 g, 25.6 mmol) wasadded-to a stirred solution of the diketone from Step 1 (6.04 g, 23.2mmol) in ethanol (95 mL). The reaction was heated to reflux and stirredovernight (17.0 hours). The reaction mixture was filtered, and thefiltrate cooled to 0° C. and filtered to give the pyrazole as a yellowsolid (4.42 g, 46%): mp 213°-215° C.; ¹ H NMR (acetone-d₆) 300 MHz 8.09(d, J=8.9 Hz, 2H) 7.75 (d, J=8.7 Hz, 2H) 7.53 (d, J=7.8Hz,1H) 7.29 (2d,1H) 7.07 (2d, 1H) 6.94 (d, J=8.1Hz, 2H) 6.92 (br s, 1H) 4.09 (s, 2H); ¹⁹F NMR (acetone-d₆) 300 MHz -62.22 (s). High resolution mass spectrumCalc'd. for C₁₇ H₁₂ F₃ N₃ O₂ S₂ : 411.0323. Found: 411.0330. ##STR329##Methyl[1-[(4-aminosulfonyl)phenyl]-1,4-dihydro-[1]benzothiopyrano[4,3-c]pyrazol-3-yl]carboxylate

Step 1

Preparation of methyl-3-(1-oxo-2-carboxy)thiochroman-4-one

A 500 mL flask was charged with thiochroman-4-one (9.84 g, 59.9 mmol),dimethyl oxalate (8.54 g, 72.3 mmol) and methanol (75 mL). The reactionwas treated with sodium methoxide (25% in methanol, 15.61 g, 72.2 mmol)and stirred at room temperature for 17.8 hours. The reaction was treatedwith 3N hydrochloric acid (30 mL) and filtered to give the diketone(13.58 g, 90%) as an orange solid: mp 94°-97° C.; ¹ H NMR (CDCl₃) 300MHz 15.94 (s, 1H) 8.01 (d, J=7.9 Hz, 1H) 7.24-7.39 (m, 3H) 4.11 (s, 2H)3.94 (s, 3H). Mass spectrum: M+=250.

Step 2

Preparation of methyl1-[4-(aminosulfonyl)phenyl]-1,4-dihydro-[1]benzothiopyrano[4,3-c]pyrazol-3-yl]carboxylate

4-Sulfonamidophenylhydrazine hydrochloride (12.06 g, 53.9 mmol) wasadded to a stirred solution of the diketone from Step 1 (12.23 g, 48.9mmol) in MeOH (250 mL). The reaction was heated to reflux and stirredfor 6.5 hours. The reaction mixture was filtered, washed with MeOH anddried under vacuum to give the pyrazole as an orange solid (17.88 g,91%): mp 265°-269° C.; ¹ H NMR (DMSO-d₆) 300 MHz 7.97 (d, J=8.5 Hz, 2H)7.69 (d, J=8.5 Hz, 2H) 7.58 (br s, 2H) 7.50 (d, J=7.9 Hz, 1H) 7.24 (t,J=7.7 Hz,1H) 7.04 (d, J=7.7 Hz, 1H) 6.76 (d, J=7.9 Hz, 1H) 4.21 (s, 2H)3.86 (s, 3H). Mass spectrum: M+H=402. ##STR330##4-[6,7-Dichloro-1,4-dihydro-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of 3-(2,3-dichlorophenylthio)propanoic acid

2,3-Dichlorothiophenol (4.94 g, 28 mmol) was placed in a flask withacrylic acid (2.11 g, 29 mmol) and stirred at 50° C. for 3 hours. Thereaction mixture was poured into 10% Na₂ CO₃ and extracted with ether.The aqueous layer was acidified with concentrated hydrochloric acid,extracted with ether, washed with brine, dried over MgSO₄, andconcentrated in vacuo to give the 3-(2,3-dichlorophenylthio)propanoicacid (3.88 g), contaminated with some acrylic acid, as a clear oil whichwas used without further purification in the next step.

Step 2

Preparation of 7,8-dichlorothiochroman-4-one

The 3-(2,3-dichlorophenylthio)propanoic acid from Step 1 (3.88 g, 15mmol) was dissolved in trifluoroacetic acid (10 mL), treated withtrifluoroacetic anhydride (5 mL) and stirred at room temperature for68.2 hours. The reaction mixture was poured into 10% Na₂ CO₃ (100 mL),extracted with ethyl acetate, washed with brine, dried over MgSO₄, andconcentrated in vacuo to give a yellow oil. The crude material waspassed through a column of silica gel eluting with 40% ethylacetate/hexane to give 7,8-dichlorothiochroman-4-one as a white solid(0.46 g, 13%): mp 93°-102° C.; ¹ H NMR (CDCl₃) 300 MHz 7.99 (d, J=8.7Hz, 1H) 7.27 (d, J=8.7 Hz, 1H) 3.25 (m, 2H) 2.97 (m, 2H). Mass spectrum:M+=233.

Step 3

Preparation of 7,8-dichloro-3-(trifluoroacetyl)thiochroman-4-one

Ethyl trifluoroacetate (0.29 g, 2.0 mmol) was placed in a round bottomflask, and dissolved in ether (12 mL). To the stirred solution was addedsodium methoxide (25%) (0.84 g, 3.9 mmol), followed by7,8-dichlorothiochroman-4-one from Step 2 (0.42 g, 1.8 mmol). Thereaction was stirred at room temperature overnight (19.4 hours) andtreated with 3N hydrochloric acid. The organic layer was collected,washed with brine, dried over MgSO₄, and concentrated in vacuo to give abrown oily solid which was used without purification in the next step.

Step 4

Preparation of4-[6,7-dichloro-1,4-dihydro-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

4-Sulfonamidophenylhydrazine hydrochloride (0.32 g, 1.4 mmol) was addedto a stirred solution of the diketone from Step 3 (0.44 g, 1.3 mmol) inethanol (10 mL). The reaction was heated to reflux and stirred overnight(19.4 hours). The reaction mixture was filtered and the filtrateconcentrated in vacuo, dissolved in ethyl acetate, washed with water andbrine, dried over MgSO₄, reconcentrated in vacuo, and passed through acolumn of silica gel (hexane/ethyl acetate) to give the pyrazole as awhite solid (0.24 g, 38%): ¹ H NMR (acetone-d₆) 300 MHz 8.08 (d, J=8.7Hz, 2H) 7.77 (d, J=8.7 Hz, 2H) 7.27 (d, J=8.5Hz, 1H) 6.95 (d,J=8.5Hz,1H) 6.79 (br s, 2H) 4.23 (s, 2H); ¹⁹ F NMR (acetone-d₆) 300 MHz-62.25 (s). High resolution mass spectrum Calc'd. for C₁₇ H₁₀ Cl₂ F₃ N₃O₂ S₂ : 479.9622. Found: 479.9565. ##STR331##4-[1,4-Dihydro-7-fluoro-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of 3-(3-fluorophenylthio)propanoic acid

3-Fluorothiophenol (5.39 g, 42 mmol) was placed in a flask with acrylicacid (3.73 g, 52 mmol) and stirred at room temperature for 20.2 hours.The reaction mixture solidified, was dissolved in ether and extractedwith 10% Na₂ CO₃. The aqueous layer was acidified with concentratedhydrochloric acid, extracted with ether, washed with brine, dried overMgSO₄, and concentrated in vacuo to give the3-(3-fluorophenylthio)propanoic acid (6.75 g), contaminated with someacrylic acid, as a white solid which was used without furtherpurification in the next step.

Step 2

Preparation of 7-fluorothiochroman-4-one

The acid from Step 1 (6.75 g, 34 mmol) was dissolved in trifluoroaceticacid (20 mL), treated with trifluoroacetic anhydride (10 mL) and stirredat room temperature for 2.2 hours. The reaction mixture was poured into10% Na₂ CO₃ (100 mL), extracted with ether, washed with brine, driedover MgSO₄, and concentrated in vacuo to give a yellow oil which waspassed through a column of silica gel with 20% ethyl acetate/hexane togive 7-fluorothiochroman-4-one as a white solid (2.09 g, 34%): mp61°-66° C.; ¹ H NMR (CDCl₃) 300 MHz 8.13 (m, 1H) 6.98 (m, 1H) 6.86 (m,1H) 3.23 (m, 2H) 2.99 (m, 2H); ¹⁹ F NMR (CDCl₃) 300 MHz -104.70 (m).Mass spectrum: M+H=183.

Step 3

Preparation of 7-fluoro-3-(trifluoroacetyl)thiochroman-4-one

Ethyl trifluoroacetate (1.04 g, 7.3 mmol) was added to solution of7-fluorothiochroman-4-one from Step 2 (1.24 g, 6.8 mmol) in ether (15mL). The reaction was treated with 25% sodium methoxide (1.86 g, 8.6mmol) and stirred at room temperature for 20.9 hours, then treated with3N hydrochloric acid (10 mL). The organic layer was collected, washedwith brine, dried over MgSO₄, concentrated in vacuo, and recrystallizedfrom dichloromethane/isooctane to give the diketone as a yellow solid(0.58 g, 31%): mp 84°-89° C.; ¹ H NMR (CDCl₃) 300 MHz 15.65 (s, 1H) 8.03(m, 1H) 7.08 (m, 1H) 6.97 (m, 1H) 3.83 (s, 2H); ¹⁹ F NMR (CDCl₃) 300 MHz-71.81 (s) -103.04 (m).

Step 4

Preparation of4-[1,4-dihydro-7-fluoro-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

4-Sulfonamidophenylhydrazine hydrochloride (1.36 g, 6.1 mmol) was addedto a stirred solution of the diketone from Step 3 (1.65 g, 5.9 mmol) inethanol (10 mL). The reaction was heated to reflux and stirred overnight(15.2 hours). The reaction mixture was filtered and the filtrate cooledin ice to give the pyrazole as a white solid (0.24 g, 38%): ¹ H NMR(acetone-d₆) 300 MHz 8.09 (d, J=8.7 Hz, 2H) 7.76 (d, J=8.7 Hz, 2H) 7.38(d, J=9.1Hz, 1H) 6.99 (m, 1H) 6.88 (m, 1H) 6.80 (br s, 2H) 4.14 (s, 2H);¹⁹ F NMR (acetone-d₆) 300 MHz: -62.25 (s) -112.68 (m). High resolutionmass spectrum Calc'd. for C₁₇ H₁₁ F₄ N₃ O₂ S₂ : 429.0229. Found:429.0205. ##STR332##4-[1,4-Dihydro-6-isopropyl-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of 3-(2-isopropylphenylthio)propanoic acid

2-Isopropylthiophenol (4.77 g, 31 mmol) was placed in a flask withacrylic acid (2.37 g, 33 mmol) and stirred at room temperature for 71.8hours. The reaction mixture solidified, was dissolved in ethyl acetateand extracted with 5% NaOH. The aqueous layer was acidified withconcentrated hydrochloric acid, extracted with ethyl acetate, dried overMgSO₄, and concentrated in vacuo to give3-(2-isopropylphenylthio)propanoic acid (6.85 g), contaminated with someacrylic acid, as a yellow solid which was used without furtherpurification in the next step.

Step 2

Preparation of 8-isopropylthiochroman-4-one

3-(2-Isopropylphenylthio)propanoic acid from Step 1 (6.85 g, 30 mmol)was dissolved in trifluoroacetic acid (20 mL), treated withtrifluoroacetic anhydride (12 mL) and stirred at room temperature (64.2hours). The reaction was concentrated in vacuo, and the residuedissolved in ethyl acetate, extracted with 5% NaOH, washed with brine,dried over MgSO₄, and concentrated in vacuo to give a brown oil whichwas passed through a column of silica gel eluted with 12% ether/hexaneto give 8-isopropylthiochroman-4-one as a brown oil (1.05 g, 17%): ¹ HNMR (CDCl₃) 300 MHz 8.01 (d, J=7.0 Hz, 1H) 7.38 (d, J=7.5 Hz, 1H) 7.17(t, J=7.8 Hz, 1H) 3.19 (m, 3H) 2.96 (m, 2H) 1.25 (d, J=7.0 Hz 6H).

Step 3

Preparation of 8-isopropyl-3-(trifluoroacetyl)thiochroman-4-one

Ethyl trifluoroacetate (0.69 g, 4.9 mmol) was added to a solution of2-isopropylthiochroman-4-one from Step 2 (0.97 g, 4.7 mmol) in ether (10mL). The reaction was treated with 25% sodium methoxide (1.08 g, 5.0mmol), stirred at room temperature for 18.2 hours and treated with 3Nhydrochloric acid (5 mL). The organic layer was collected, washed withbrine, dried over MgSO₄ and concentrated in vacuo to give the diketoneas a brown oil (0.80 g) which was used without further purification inthe next step.

Step 4

Preparation of4-[1,4-dihydro-6-isopropyl-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

4-Sulfonamidophenylhydrazine hydrochloride (0.69 g, 3.1 mmol) was addedto a stirred solution of the diketone from Step 3 (0.83 g, 2.7 mmol) inethanol (10 mL). The reaction was heated to reflux, stirred overnight(16.1 hours) and concentrated in vacuo. The residue was dissolved inethyl acetate washed with water, washed with brine, dried over MgSO₄,reconcentrated in vacuo and passed through a column of silica gel with20% ethyl acetate/hexane to give the pyrazole as a brown solid (0.43 g,35%): mp 183°-186° C. ¹ H NMR (acetone-d₆) 300 MHz 8.10 (d, J=8.7 Hz,2H) 7.71 (d, J=8.5 Hz, 2H) 7.35 (d, J=7.9Hz, 1H) 7.04 (t, J=7.9 Hz, 1H)6.79 (m, 3H) 4.04 (s, 2H) 3.46 (m, 1H) 1.28 (d, J=6.8 Hz, 6H); ¹⁹ F NMR(acetone-d₆) 300 MHz -62.19 (s) -112.68 (m). High resolution massspectrum Calc'd. for C₂₀ H₁₈ F₃ N₃ O₂ S₂ : 453.0793. Found: 453.0848.##STR333##4-[1,4-Dihydro-7,8-dimethoxy-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of 3-(3,4-dimethoxyphenylthio)propanoic acid

3,4-Dimethoxythiophenol (5.00 g, 29 mmol) was placed in a flask withacrylic acid (2.27 g, 32 mmol) and stirred at room temperature for 22.4hours. The reaction mixture solidified, was dissolved in ethyl acetateand extracted with 10% Na₂ CO₃. The aqueous layer was acidified withconcentrated hydrochloric acid, extracted with ether, dried over MgSO₄,and concentrated in vacuo to give 3-(3,4-dimethoxyphenylthio)propanoicacid (5.39 g, 76%), contaminated with some acrylic acid, as a whitesolid which was used without further purification in the next step: mp62°-64° C.; ¹ H NMR (CDCl₃) 300 MHz 9.80 (br s, 1H) 7.01 (d, J=8.3 Hz,1H) 6.98 (s, 1H) 6.82 (d, J=8.3 Hz, 1H) 3.87 (s, 3H) 3.86 (s, 3H) 3.06(t, J=7.3 Hz, 2H) 2.63 (t, J=7.3 Hz, 2H). Mass spectrum: M+=242.

Step 2

Preparation of 6,7-dimethoxythiochroman-4-one

The acid from Step 1 (5.23 g, 22 mmol) was dissolved in trifluoroaceticacid (20 mL), treated with trifluoroacetic anhydride (12 mL) and stirredat room temperature (10 minutes). The reaction was poured into 10% Na₂CO₃ (100 mL) and filtered to collect 6,7-dimethoxythiochromanone as ayellow solid (1.12 g, 23%). The filtrate was washed with brine, driedover MgSO₄, concentrated in vacuo and recrystallized from ethylacetate/hexane to give more 6,7-dimethoxythiochromanone (1.77 g, 37%) asan orange solid: mp 138°-143° C.; ¹ H NMR (CDCl₃) 300 MHz 7.60 (s, 1H)6.68 (s, 1H) 3.91 (s, 3H) 3.89 (s, 3H) 3.19 (m, 2H) 2.93 (m, 3H). Massspectrum: M+=224.

Step 3

Preparation of 6,7-dimethoxy-3-trifluoroacetylthiochroman-4-one

Ethyl trifluoroacetate (0.84 g, 5.9 mmol) was dissolved intetrahydrofuran (20 mL), and treated with 25% sodium methoxide (1.68 g,7.8 mmol). To the stirred solution was added6,7-dimethoxythiochroman-4-one from Step 2 (1.12 g, 5.0 mmol). Thereaction was stirred at room temperature for 87.5 hours, treated with 3NHCl (25 mL) and filtered to give an orange solid (1.04 g, 65%): mp148°-151° C.; ¹ H NMR (CDCl₃) 300 MHz 16.05 (s, 1H), 7.48 (s, 1H) 6.78(s, 1H) 3.94 (s, 3H) 3.92 (s, 3H) 3.83 (s, 2H); ¹⁹ F NMR (CDCl₃) 300 MHz-71.06 (s). Mass spectrum: M+H=321.

Step 4

Preparation of4-[1,4-dihydro-7,8-dimethoxy-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

4-Sulfonamidophenylhydrazine hydrochloride (0.76 g, 3.4 mmol) was addedto a stirred solution of the diketone from Step 3 (1.00 g, 3.1 mmol) inethanol (20 mL). The reaction was heated to reflux and stirred overnight(15.5 hours). The reaction mixture was filtered and the filtrateconcentrated in vacuo, dissolved in ethyl acetate, washed with water andbrine, dried over MgSO₄, reconcentrated in vacuo, and recrystallizedfrom ethyl acetate/isooctane to give the pyrazole as a yellow solid(0.72 g, 49%): mp 164°-168° C.; ¹ H NMR (acetone-d₆) 300 MHz 8.13 (d,J=8.7 Hz, 2H) 7.77 (d, J=8.5 Hz, 2H) 7.06 (s, 1H) 6.82 (br s, 2H) 6.36(s, 1H) 4.04 (s, 2H) 3.85 (s, 3H) 3.85 (s, 3H); ¹⁹ F NMR (acetone-d₆)300 MHz -62.20 (s). High resolution mass spectrum Calc'd. for C₁₉ H₁₆ F₃N₃ O₄ S₂ : 471.0534. Found: 471.0534. ##STR334##4-[1,4-Dihydro-7-methoxy-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of 3-(3-methoxyphenylthio)propanoic acid

3-Methoxythiophenol (5.70 g, 41 mmol) was placed in a flask with acrylicacid (2.36 g, 33 mmol) and stirred at room temperature for 113.8 hours.The reaction mixture was dissolved in ether and extracted with 10% Na₂CO₃. The aqueous layer was acidified with concentrated HCl, extractedwith ether, dried over MgSO₄, and concentrated in vacuo to give the3-(3-methoxyphenylthio)propanoic acid (2.55 g , 37%) as a white solid:mp 39°-42° C.; ¹ H NMR (CDCl₃) 300 MHz 7.21 (m, 1H) 6.91 (m, 2H) 6.77(d, J=8.3 Hz, 1H) 3.79 (s, 3H) 3.16 (t, J=7.5 Hz, 2H) 2.68 (t, J=7.3 Hz,2H).

Step 2

Preparation of 7-methoxythiochroman-4-one

The acid from Step 1 (2.55 g, 12 mmol) was dissolved in trifluoroaceticacid (10 mL), treated with trifluoroacetic anhydride (5 mL) and stirredat room temperature (10 minutes). The reaction was poured into 10% Na₂CO₃ (60 mL), extracted with ether, washed with brine, dried over MgSO₄,and concentrated in vacuo to give a red oil which was passed through acolumn of silica gel with 50% ether/hexane to give7-methoxythiochroman-4-one as an orange solid (1.18 g, 51%): mp 49°-51°C.; ¹ H NMR (CDCl₃) 300 MHz 8.06 (d, J=8.9 Hz, 1H) 6.72 (m, 2H) 3.83 (s,3H) 3.20 (m, 2H) 2.95 (m, 2H). Mass spectrum: M+H=195.

Step 3

Preparation of 7-methoxy-3-(trifluoroacetyl)thiochroman-4-one

7-Methoxythiochroman-4-one from Step 2 (1.13 g, 5.8 mmol) and ethyltrifluoroacetate (0.87 g, 6.1 mmol) were dissolved in ether (15 mL),treated with 25% sodium methoxide (2.13 g, 9.9 mmol), stirred at roomtemperature for 23.0 hours, and treated with 3N HCl. The organic layerwas collected, washed with brine, dried over MgSO₄, concentrated invacuo and recrystallized from dichloromethane/isooctane to give thediketone as a yellow solid (0.60 g, 35%): mp 93°-98° C.; ¹ H NMR (CDCl₃)300 MHz 15.92 (s, 1H) 7.96 (d, J=8.9 Hz, 1H) 6.82 (m, 2H) 3.87 (s, 3H)3.82 (s, 2H); ¹⁹ F NMR (CDCl₃) 300 MHz -71.43 (s). Mass spectrum:M+H=291.

Step 4

Preparation of4-[1,4-dihydro-7-methoxy-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

4-Sulfonamidophenylhydrazine hydrochloride (0.46 g, 2.1 mmol) was addedto a stirred solution of the diketone from Step 3 (0.57 g, 2.0 mmol) inethanol (5 mL). The reaction was heated to reflux and stirred overnight(21.5 hrs). The reaction mixture was filtered while hot to give thepyrazole as a yellow solid (0.63 g, 72%): mp 201°-206° C.; ¹ H NMR(acetone-d₆) 300 MHz 8.08 (d, J=8.7 Hz, 2H) 7.73 (d, J=8.7 Hz, 2H) 7.09(d, J=2.6 Hz, 1H) 6.84 (d, J=8.7 Hz, 1H) 6.80 (br s,1H) 6.66 (dd, J=2.6Hz J=8.9 Hz, 1H) 4.07 (s, 2H) 3.83 (s, 3H); ¹⁹ F NMR (acetone-d₆) 300MHz -62.24 (s). High resolution mass spectrum Calc'd. for C₁₈ H₁₄ F₃ N₃O₃ S₂ : 441.0429. Found: 441.0457. ##STR335##4-[1,4-Dihydro-7-methyl-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of 3-(3-methoxyphenylthio)propanoic acid

3-Thiocresol (9.71 g, 78 mmol) was placed in a flask with acrylic acid(5.65 g, 78 mmol) and stirred at room temperature for 62.9 hours. Thereaction mixture solidified and was dissolved in ether and extractedwith 10% Na₂ CO₃. The aqueous layer was acidified with concentratedhydrochloric acid, extracted with ether, washed with brine, dried overMgSO₄ and concentrated in vacuo to give the3-(3-dimethylphenylthio)propanoic acid (10.13 g , 66%) contaminated withsome acrylic acid as a white solid, which was used without furtherpurification in the next step.

Step 2

Preparation of 7-methylthiochroman-4-one

3-(3-Methylphenylthio)propanoic acid from Step 1 (10.12 g, 52 mmol) wasdissolved in trifluoroacetic acid (20 mL), treated with trifluoroaceticanhydride (10 mL) and stirred at room temperature for 1.9 hours. Thereaction was poured into 10% Na₂ CO₃ (100 mL), extracted with ether,washed with brine, dried over MgSO₄, and concentrated in vacuo to givean orange oil which was passed through a column of silica gel elutingwith 8% ether/hexane to give 7-methylthiochroman-4-one (2.97 g, 32%) asa yellow oil: ¹ H NMR (CDCl₃) 300 MHz 7.97 (d, J=8.1 Hz, 1H) 7.06 (s,1H) 6.97 (d, J=7.7 Hz, 1H) 3.17 (m, 2H) 2.95 (m, 2H) 2.31 (s, 3H). Massspectrum: M+H=179.

Step 3

Preparation of 7-methyl-3-(trifluoroacetyl)thiochroman-4-one

7-Methylthiochroman-4-one from Step 2 (2.92 g, 16 mmol) and ethyltrifluoroacetate (2.45 g, 17 mmol) were dissolved in ether (20 mL),treated with 25% sodium methoxide (4.60 g, 21 mmol), stirred at roomtemperature for 15.0 hours and treated with 3N hydrochloric acid (15mL). The organic layer was collected, washed with brine, dried overMgSO₄, concentrated in vacuo, and recrystallized fromdichloromethane/isooctane to give the diketone as a yellow solid (3.05g, 68%): mp 68°-72° C.; ¹ H NMR (CDCl₃) 300 MHz 15.73 (s, 1H) 7.89 (d,J=8.1 Hz, 1H) 7.17 (s, 1H) 7.09 (d, J=8.1 Hz, 1H) 3.80 (s, 2H) 2.37 (s,3H); ¹⁹ F NMR (CDCl₃) 300 MHz -71.75 (s). Mass spectrum: M+H=275.

Step 4

Preparation of4-[1,4-dihydro-7-methyl-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

4-Sulfonamidophenylhydrazine hydrochloride (1.21 g, 5.4 mmol) was addedto a stirred solution of the diketone from Step 3 (1.41 g, 5.1 mmol) inethanol (20 mL). The reaction was heated to reflux and stirred overnight(15.8 hours). The reaction mixture was filtered and the filtrateconcentrated in vacuo, dissolved in ethyl acetate, washed with water andbrine, dried over MgSO₄, reconcentrated in vacuo, and recrystallizedfrom ethyl acetate/isooctane to give the pyrazole as a yellow solid(1.14 g, 52%): mp 251°-252° C.; ¹ H NMR (acetone-d₆) 300 MHz 8.08 (d,J=8.7 Hz, 2H) 7.73 (d, J=8.7 Hz, 2H) 7.36 (s, 1H) 6.79 (m, 4H) 4.06 (s,2H) 2.29 (s, 3H); ¹⁹ F NMR (acetone-d₆) 300 MHz -62.22(s). Highresolution mass spectrum Calc'd. for C₁₈ H₁₄ F₃ N₃ O₂ S₂ : 425.0480.Found: 425.0470. ##STR336##4-[7-Chloro-1,4-dihydro-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of 3-(3-chlorophenylthio)propanoic acid

Acrylic acid (2.66 g, 37 mmol) and 3-chlorothiophenol (4.85 g, 34 mmol)were dissolved in ether (15 mL) and stirred at room temperature for 88.0hours. The reaction mixture solidified, was dissolved in ether andextracted with 5% NaOH. The aqueous layer was acidified withconcentrated hydrochloric acid, extracted with ether, washed with brine,dried over MgSO₄, and concentrated in vacuo to give the3-(3-chlorophenylthio)propanoic acid (2.20 g, 34%): ¹ H NMR (acetone-d₆)300 MHz 7.33-7.40 (m, 3H) 7.24 (m, 1H) 3.25 (t, J=7.1 Hz, 2H) 2.67 (t,J=7.1 Hz, 2H). Mass spectrum: M+H=217.

Step 2

Preparation of 7-chlorothiochroman-4-one

3-(3-Chlorophenylthio)propanoic acid from Step 1 (2.18 g, 10 mmol) wasdissolved in trifluoroacetic acid (10 mL), treated with trifluoroaceticanhydride (6 mL) and stirred at room temperature for 67.8 hours. Thereaction was concentrated in vacuo and the residue dissolved indichloromethane, extracted with 5% NaOH, dried over MgSO₄, andreconcentrated in vacuo to give a brown oil. The crude oil was passedthrough a column of silica gel with 10% ether/hexane to give a mixtureof 7-chlorothiochroman-4-one and 5-chlorothiochroman-4-one as a yellowoil (1.30 g) which was carried on to the next step without furtherpurification.

Step 3

Preparation of 7-chloro-3-(trifluoroacetyl)thiochroman-4-one

Ethyl trifluoroacetate (1.02 g, 7.2 mmol) was placed in a round bottomflask and dissolved in ether (10 mL). To the stirred solution was added25% sodium methoxide (1.80 g, 8.3 mmol) followed by7-chlorothiochroman-4-one from Step 2 (1.30 g, 6.5 mmol). The reactionwas stirred at room temperature overnight (17.3 hrs) and treated with 3Nhydrochloric acid (5 mL). The organic layer was collected, washed withbrine, dried over MgSO₄, concentrated in vacuo, and recrystallized fromether/hexane to give the diketone (0.61 g, 32%) as a yellow solid: mp64°-71° C.; ¹ H NMR (CDCl₃) 300 MHz 15.53 (s, 1H) 7.92 (d, J=8.5 Hz, 1H)7.36 (s, 1H) 7.25 (d, J=8.7 Hz, 1H) 3.82 (s, 2H); ¹⁹ F NMR (CDCl₃) 300MHz -71.97 (s). Mass spectrum: M+=294.

Step 4

Preparation of4-[7-chloro-1,4-dihydro-3-(trifluoromethyl)-[1]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

4-Sulfonamidophenylhydrazine hydrochloride (0.43 g, 1.9 mmol) was addedto a stirred solution of the diketone from Step 3 (0.55 g, 1.9 mmol) inethanol (6 mL). The reaction was heated to reflux and stirred for 18.9hours. The reaction mixture was cooled and filtered to give the pyrazoleas a yellow solid (0.15 g, 18%): mp 237°-238° C.; ¹ H NMR (acetone-d₆)300 MHz 8.09 (d, J=8.7 Hz, 2H) 7.77 (d, J=8.7 Hz, 2H) 7.59 (d, J=2.0 Hz,1H) 7.10 (dd, J=8.5 Hz J=2.0Hz, 1H) 6.96 (d, J=8.5 Hz, 1H) 6.81 (br s,2H) 4.14 (s, 2H); ¹⁹ F NMR (acetone-d₆) 300 MHz -62.25 (s). Highresolution mass spectrum Calc'd. for C₁₇ H₁₁ ClF₃ N₃ O₂ S₂ : 444.9933.Found: 444.9874. ##STR337##4-[1,5-Dihydro-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of 3-(trifluoroacetyl)isothiochroman-4-one

Ethyl trifluoroacetate (3.67 g, 25.8 mmol) was dissolved intetrahydrofuran (15 mL) and treated with 25% sodium methoxide (6.46 g,29.9 mmol) followed by a solution of isothiochroman-4-one (4.15 g, 25.3mmol) in tetrahydrofuran (15 mL). The reaction was stirred at roomtemperature for 70.8 hours and treated with 3N hydrochloric acid (10mL). The organic layer was collected, washed with brine, dried overMgSO₄, concentrated in vacuo, and passed through a column of silica geleluting with 40% ethyl acetate/hexane to give a brown solid (5.40 g,82%): ¹ H NMR (CDCl₃) 300 MHz 15.30 (s, 1H) 7.99 (d, J=7.9 Hz, 1H) 7.54(m, 1H) 7.43 (m, 1H) 7.23 (m, 1H) 3.81 (s, 3H).

Step 2

Preparation of4-[1,5-dihydro-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

4-Sulfonamidophenylhydrazine hydrochloride (0.81 g, 3.6 mmol) was addedto a stirred solution of the diketone from Step 1 (0.83 g, 3.2 mmol) inethanol (10 mL). The reaction was heated to reflux and stirred 2.1hours. The reaction mixture was filtered and the filtrate concentratedin vacuo. The residue was dissolved in ethyl acetate, washed with waterand with brine, dried over MgSO₄, reconcentrated in vacuo, and passedthrough a column of silica gel with 40% ethyl acetate to give thepyrazole (0.15 g, 11%): mp 230°-232° C.; ¹ H NMR (acetone-d₆) 300 MHz8.09 (d, J=8.7 Hz, 2H) 7.85 (d, J=8.9 Hz, 2H) 7.53 (d, J=7.7Hz, 1H) 7.40(t, J=7.5 Hz,1H) 7.21 (t, J=7.7 Hz,1H) 6.93 (d, J=7.9 Hz, 1H) 6.79 (br s,2H) 4.16 (s, 2H); ¹⁹ F NMR (acetone-d₆)) 300 MHz -62.94(s). Highresolution mass spectrum Calc'd. for C₁₇ H₁₂ F₃ N₃ O₂ S₂ : 411.0323.Found: 411.0324. ##STR338##4-[1,5-Dihydro-7-methyl-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of S-(3-methylbenzyl)-isothiouronium chloride

Thiourea (26.19 g, 344 mmol) was added to a solution ofα-chloro-m-xylene (48.21 g, 343 mmol) in methanol (50 mL). The reactionwas heated to reflux and additional methanol (10 mL) was added todissolve all of the thiourea. After 64.3 hours, the reaction wasfiltered and dried under vacuum to give a white solid (68.15 g, 92%): mp182°-186° C.; ¹ H NMR (DMSO-d₆) 300 MHz 9.34 (br s, 4H) 7.22 (m, 3H)7.12 (m, 1H) 4.48 (s, 2H) 2.27 (s, 3H).

Step 2

Preparation of 3-(3-methylphenylthio)propanoic acid

A 250 mL flask was charged with the thiouronium salt from Step 1 (10.99g, 51 mmol), sodium chloroacetate (8.86 g, 76 mmol), ethanol (95 mL) andwater (10 mL). After heating to reflux, a solution of NaOH (9.05 g, 226mmol) in water (50 mL) was added to the reaction dropwise over sevenminutes. After stirring for 3.6 hours. the reaction was acidified withconcentrated hydrochloric acid, extracted with ether, washed with brine,dried over MgSO₄ and concentrated in vacuo to give a white solid (9.95g, 100%): mp 73°-75.5° C.; ¹ H NMR (CDCl₃) 300 MHz 7.16 (m, 4H) 3.83 (s,2H) 3.12 (s, 2H) 2.35 (s, 3H). Mass spectrum: M+=196.

Step 3

Preparation of 7-methylisothiochroman-4-one

The acid from Step 2 (6.06 g, 31 mmol) was dissolved in trifluoroaceticacid (11 mL), treated with trifluoroacetic anhydride (5 mL) and stirredat room temperature for 0.33 hours. The reaction was poured into 10% Na₂CO₃ (100 mL), extracted with ether, washed with brine, dried over MgSO₄,concentrated in vacuo, and recrystallized from ether/hexane to give7-chloroisothiochroman-4-one (2.25 g, 41%) as a white solid: mp79.5°-82° C.; ¹ H NMR (CDCl₃) 300 MHz 7.97 (d, J=8.1 Hz, 1H) 7.17 (d,J=8.1 Hz, 1H) 7.00 (s, 1H) 3.87 (s, 2H) 3.52 (s, 2H) 2.37 (s, 3H). Massspectrum: M+H=179.

Step 4

Preparation of 7-methyl-3-(trifluoroacetyl)isothiochroman-4-one

Ethyl trifluoroacetate (1.80 g, 12.7 mmol) was placed in a round bottomflask and dissolved in ether (10 mL). To the stirred solution was added25% sodium methoxide (3.90 g, 18.0 mmol) followed by7-chloroisothiochroman-4-one from Step 3 (2.25 g, 12.6 mmol) dissolvedin ether (10 mL) and tetrahydrofuran (10 mL). The reaction was stirredat room temperature for 24.6 hours and treated with 3N hydrochloricacid. The organic layer was collected, washed with brine, dried overMgSO₄, concentrated in vacuo and passed through a column of silica gelwith 20% ether/hexane to give the diketone (1.93 g, 56%) as a brownsolid: ¹ H NMR (CDCl₃) 300 MHz 15.45 (s, 1H) 7.88 (d, J=8.1 Hz, 1H) 7.25(d, J=8.1 Hz, 1H) 7.06 (s, 1H) 3.77 (s, 2H) 2.43 (s, 2H); ¹⁹ F NMR(CDCl₃) 300 MHz: -72.76 (s). Mass spectrum: M+H=275.

Step 5

Preparation of4-[1,5-dihydro-7-methyl-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

4-Sulfonamidophenylhydrazine hydrochloride (1.68 g, 7.5 mmol) was addedto a stirred solution of the diketone from Step 4 (1.93 g, 7.0 mmol) inethanol (15 mL). The reaction was heated to reflux and stirred for 15.2hours. The reaction mixture was concentrated in vacuo and the residuedissolved in ethyl acetate, washed with water and with brine, dried overMgSO₄, reconcentrated in vacuo and recrystallized from ethylacetate/isooctane to give the pyrazole as a brown solid (1.48 g, 49%):mp 253°-255° C.; ¹ H NMR (acetone-d₆) 300 MHz 8.08 (d, J=8.7 Hz, 2H)7.83 (d, J=8.7 Hz, 2H) 7.35 (s, 1H) 7.02 (d, J=8.1 Hz,1H) 6.78 (m, 3H)4.11 (s, 2H) 2.34 (s, 3H); ¹⁹ F NMR (acetone-d₆) 300 MHz -62.94 (s).High resolution mass spectrum Calc'd. for C₁₈ H₁₄ F₃ N₃ O₂ S₂ :426.0558. Found: 426.05554. ##STR339## 1,5-Dihydro-1-[4-(methylsulfonyl)phenyl]-7-methyl-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazole

Step 1

Preparation of1-[4-methylsulfonylphenyl]-7-methyl-3-(trifluoromethyl)-1,5-dihydro-[2]benzothiopyrano[4,3-c]pyrazole

4-(Methylsulfonyl)phenylhydrazine (1.23 g, 6.6 mmol) was converted tothe hydrochloride salt by stirring with a 4N solution of hydrochloricacid in dioxane (10 mL) for 25 minutes. The dioxane was removed invacuo, and the 4-(methylsulfonyl)phenylhydrazine hydrochloride wascombined with the diketone (Example 17, Step 4) (1.12 g, 2.9 mmol) andethanol (20 mL), heated to reflux and stirred for 15.5. hours. Thereaction mixture was filtered while hot and the filtrate wasconcentrated in vacuo. The residue was dissolved in ethyl acetate,washed with water and with brine, dried over MgSO₄, reconcentrated invacuo, and passed through a column of silica gel eluting with 12% ethylacetate/hexane to give the pyrazole (0.31 g, 18%) as a yellow solid: mp207°-209° C.; ¹ H NMR (acetone-d₆) 300 MHz 8.14 (d, J=8.7 Hz, 2H) 7.92(d, J=8.9 Hz, 2H) 7.35 (s, 1H) 7.35 (d, J=8.1 Hz, 1H) 6.83 (d, J=7.9 Hz,1H) 4.11 (s, 2H) 3.23 (s, 3H) 2.34 (s, 3H); ¹⁹ F NMR (acetone-d₆) 300MHz -62.97 (s). High resolution mass spectrum Calc'd. for C₁₉ H₁₅ F₃ N₂O₂ S₂ : 424.0527. Found: 424.0524. ##STR340##4-[7-Chloro-1,5-dihydro-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of S-(3-chlorobenzyl)isothiouronium chloride

3-Chlorobenzyl chloride (24.2 g, 0.15 mol) and thiourea (11.4 g, 0.15mol) were dissolved in methanol (70 mL) and heated to reflux for 16hours. The reaction was cooled to room temperature and a precipitateformed. Ether (150 mL) was added to complete the precipitation ofcompound. The crystals were isolated by filtration and washed with ether(100 mL). After drying in vacuo, 31.9 g (90%) of pureS-(3-chlorobenzyl)-isothiouronium chloride was obtained: ¹ H NMR (CD₃OD) δ=4.43p (s, 2H), 7.36p (s, 3H), 7.47p (s, 1H).

Step 2

Preparation of 3-chlorobenzylmercaptoacetic acid

S-(3-Chlorobenzyl)-isothiouronium chloride from Step 1 (11.86 g, 50mmol) and chloroacetic acid (7.1 g, 75 mmol) were dissolved in ethanol(100 ml) and heated to 80° C. in a 4-neck flask equipped with nitrogeninlet, condenser and addition funnel. A solution of NaOH (10 g) in H₂ O(100 mL) and ethanol (50 mL) was added dropwise over 1 hour to this hotsolution. The reaction was heated to 100° C. for 4 hours. The reactionwas cooled to room temperature, acidified with concentrated hydrochloricacid (45 mL) and extracted with ether (500 mL). The organic layer waswashed with brine (300 ml), dried over MgSO₄ and concentrated in vacuoto yield 10.84 g (100%) of 3-chlorobenzylmercaptoacetic acid which wasused without further purification: ¹ H NMR (CDCl₃) δ=3.08p (s, 2H),3.80p (s, 2H), 7.23p (m, 3H), 7.34p (s, 1H), 9.07p (broad s, 1H).

Step 3

Preparation of 7-chloroisothiochroman-4-one

3-Chlorobenzylmercaptoacetic acid from Step 2 (3.35 g) was dissolved intrifluoroacetic acid (50 mL). Trifluoroacetic acid anhydride (25 mL) wasadded and the reaction stirred at reflux, under a nitrogen atmospherefor 16 hours. The solution was carefully poured into 10% Na₂ CO₃solution (500 mL) which was stirring vigorously. The organics wereextracted into ether (500 mL) and washed with brine (300 mL), dried overMgSO₄ and concentrated in vacuo. The resulting brown solid was purifiedby silica gel chromatography eluting with a 0-10% gradient of ethylacetate in hexane to yield 7-chloroisothiochroman-4-one (1.57 g, 51%): ¹H NMR (CDCl₃) δ=3.49p (d, 2H, J=0.8 Hz) , 3.8p (s, 2H) , 7:16p (m, 1H) ,7.3p (dd, 1H, J=2.0, 8.4 Hz) , 7.96p (d, 1H, J=8.5 Hz).

Step 4

Preparation of 7-chloro-3-(trifluoroacetyl)isothiochroman-4-one

7-Chloroisothiochroman-4-one from Step 3 (0.3 g, 1.5 mmol) was dissolvedin tetrahydrofuran (15 mL) and cooled to -78° C. A solution of sodiumbistrimethylsilyl amide (1.5 mL of a 1.0M tetrahydrofuran solution) wasadded and the reaction stirred for 0.5 hours at -78° C. Trifluoroacetylimidazole (0.21 mL, 1.8 mmol) was added and the reaction was warmed toroom temperature and stirred under a nitrogen atmosphere for 16 hours.1N Hydrochloric acid (100 mL) was added to the reaction followed byextraction with ether (150 mL). The organics were washed with brine (75mL), dried over MgSO₄ and concentrated in vacuo. The resulting yellowoil was used in the next step without further purification.

Step 5

Preparation of4-[7-chloro-1,5-dihydro-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

A mixtrue of the diketone from Step 4 (1.51 mmol) and4-sulphonamidophenylhydrazine hydrochloride (0.41 g, 1.8 mmol) wasdissolved in ethanol (50 mL) and heated to reflux for 16 hours. Thereaction was concentrated in vacuo and the resulting solid was dissolvedin ethyl acetate (200 mL). The organics were washed with water (200 mL)and with brine (150 mL), dried over MgSO₄ and concentrated in vacuo. Theresulting oil was chromatographed on silia gel eluting with a gradientof ethyl acetate (from 10-50%) in hexane to yield pure tricyclicpyrazole (0.25 g, 40%): mp 241°-242° C.; ¹ H NMR (acetone-d₆) δ=4.18p(s, 2H), 6.79p (s, 2H), 6.94p (d, 1H, J=8.5 Hz), 7.26p (dd, 1H, J=2.2,8.4 Hz), 7.6p (d, 1H, J=2.2 Hz), 7.83p (dd, 2H, J=2.1, 6.9 Hz), 8.1p(dd, 2H, J=2.1, 6.7 Hz); ¹⁹ F NMR (acetone-d₆) δ=-62.94p (s, 3F).##STR341##4-[1,5-Dihydro-7-methoxy-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of S-(3-methoxyphenylmethyl)isothiouronium chloride

A solution of 3-methoxybenzyl chloride (15.65 g, 0.1 mol) and thiourea(7.6 g, 0.1 mol) were dissolved in 40 mL of ethanol and heated to refluxfor 16 hours, during this time the isothiouronium salt crystallized. Thethiouronium chloride was isolated by filtration and recrystallized fromether and ethanol (21.85 g, 94%, mp 172.5°-174.0° C.). This material wasused directly in the next step.

Step 2

Preparation of 3-methoxybenzylmercaptoacetic acid

The thiouronium chloride from Step 1 (20.00 g, 86 mmol) and chloroaceticacid (11.07 g, 95 mmol) were dissolved in ethanol (100 mL) and heated to80° C. in a 4-neck flask equipped with nitrogen inlet, condenser andaddition funnel. A solution of NaOH (10 g) in water (100 mL) and ethanol(50 mL) was added dropwise over 1 hour to the hot solution. The reactionwas heated to 100° C. for 4 hours. The reaction was cooled to roomtemperature, acidified with concentrated hydrochloric acid (45 mL), andextracted with ether (500 mL). The organic layer was washed with brine(300 mL), dried over MgSO₄ and concentrated in vacuo to yield an oilthat was vacuum distilled to provide 16.41 g (90%) of pure acid: bp160°-170° C. at 0.2 mm; ¹ H NMR (CDCl₃ /300 MHz) 3.1p (s, 2H), 3.8p (s,3H), 3.82p (s, 2H), 6.8p (m, 1H), 6.91p (s, 1H), 6.96p (m, 1H), 7.23p(t, 1H, J=7.7 Hz), 8.33p (broad s, 1H), 11.1(brs, 1H).

Step 3

Preparation of 7-methoxyisothiochroman-4-one

3-methoxybenzylmercaptoacetic acid from Step 2 (10.82 g) was dissolvedin trifluoroacetic acid (50 mL). Trifluoroacetic acid anhydride (25 mL)was added and the reaction stirred under a nitrogen atmosphere for 0.25hours. At this time, TLC showed no starting material. The solution wascarefully poured into 10% Na₂ CO₃ solution (500 mL) which was stirringvigorously. The organics were extracted into ether (500 mL) and washedwith brine (300 mL), dried over MgSO₄ and concentrated in vacuo. Theresulting brown solid was purified by silica gel chromatography elutingwith 20% ethyl acetate in hexane to yield 7-methoxyisothiochroman-4-one(4.84 g, 49%): ¹ H NMR (CDCl₃) δ=3.48p (t, 2H, J=0.8 Hz), 3.83p (s, 3H),3.84p (s, 2H), 6.6p (d, 1H, J=2.4 Hz), 6.83p (dd, 1H, J=2.4, 8.9 Hz),8.0p (d, H, J=8.9 Hz).

Step 4

Preparation of 7-methoxy-3-(trifluoroacetyl)-isothiochroman-4-one

7-Methoxyisothiochroman-4-one from Step 3 (0.58 g, 3.0 mmol) wasdissolved in tetrahydrofuran (30 mL) and cooled to -78° C. A solution ofsodium bistrimethylsilylamide (3.0 mL of a 1.0M tetrahydrofuransolution) was added and the reaction stirred for 0.5 hours at -78° C.Trifluoroacetyl imidazole (0.41 mL, 3.6 mmol) was added and the reactionwas warmed to room temperature and stirred under a nitrogen atmospherefor 16 hours. At this time, 1N hydrochloric acid (200 mL) was added tothe reaction followed by extraction with ether (250 mL). The organicswere washed with brine (150 mL), dried over MgSO₄ and concentrated invacuo. The resulting yellow oil (0.42 g, 48%) was used without furtherpurification.

Step 5

Preparation of4-[1,5-dihydro-7-methoxy-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

A solution of the dione from Step 4 (0.42 g, 1.4 mmol) and4-sulphonamidophenylhydrazine hydrochloride (0.42 g, 1.8 mmol) weredissolved in ethanol (50 mL) and heated to reflux for 16 hours. Thereaction was concentrated in vacuo and the resulting solid was dissolvedin ethyl acetate (200 mL). The organics were washed with H₂ O (200 mL)followed by brine (150 ml), dried over MgSO₄ and concentrated in vacuo.The resulting oil was chromatographed on silica gel eluting with agradient of ethyl acetate (from 20-50%) in hexane to yield puretricyclic pyrazole (0.25 g, 41%): mp 268°-270° C.; ¹ H NMR (acetone-d₆)δ=3.84p (s, 3H), 4.12p (s, 2H), 6.8p (m, 3H), 7.1p (d, 1H, J=2.4 Hz),7.81p (d, 2H, J=6.6 Hz), 7.82p (s, 2H), 8.08p (dd, 2H, J=1.9, 6.6 Hz);¹⁹ F NMR (acetone-d₆) δ=-62.9p (s, 3F). ##STR342##4-[7-Chloro-1,5-dihydro-3-trifluoromethylthieno[3',2':4,5]thiopyrano[3,2-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of S-(5-chloro-2-thienylmethyl)-isothiouronium chloride

2-Chloro-5-(chloromethyl)thiophene (14.5 g, 87 mmol) and thiourea (6.6g, 87 mol) were dissolved in methanol (30 mL) and heated to reflux for16 hours. The reaction was cooled to room temperature and a precipitateformed. Ether (150 mL) was added to complete the precipitation ofcompound. The crystals were isolated by filtration and washed with ether(100 mL). After drying in vacuo, 19.0 g (90%) of pureS-(5-chloro-2-thienylmethyl)-isothiouronium chloride were obtained: ¹ HNMR (CD₃ OD) δ=4.83p (s, 2H), 6.87p (d, 1H, J=3.8 Hz), 6.96p (d, 1H,J=3.2 Hz).

Step 2

Preparation of 5-chloro-2-thienylmethylmercaptoacetic acid

The compound from Step 1 (12.16 g, 50 mmol) and chloroacetic acid (7.1g, 75 mmol) were dissolved in ethanol (100 mL) and heated to 80° C. in a4-neck flask equipped with nitrogen inlet, condenser and additionfunnel. A solution of NaOH (10 g) in water (100 mL) and ethanol (50 mL)was added dropwise over 1 hour to the hot solution. The reaction washeated to 100° C. for 4 hours. The reaction was cooled to roomtemperature, acidified with concentrated hydrochloric acid (45 mL) andextracted with ether (500 mL). The organic layer was washed with brine(300 mL), dried over MgSO₄ and concentrated in vacuo to yield 11.14 g(100%) of pure acid which was used without further purification: ¹ H NMR(CDCl₃) δ=3.2p (s, 2H), 3.98p (s, 2H), 6.73p (d, 1H, J=3.6 Hz), 6.77p(d, 1H, J=3.8 Hz).

Step 3

Preparation of 6-chloro-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-one

The acid from Step 2 (4.45 g) was dissolved in trifluoroacetic acid (45mL). Trifluoroacetic acid anhydride (20 mL) was added and the reactionwas stirred under a nitrogen atmosphere for 0.25 hours. At this time,TLC showed no starting material. The solution was carefully poured into10% Na₂ CO₃ solution (600 mL) which was stirring vigorously. Theorganics were extracted into ethyl acetate (500 mL), washed with brine(300 mL), dried over MgSO₄ and concentrated in vacuo. The resultingbrown solid was purified by SiO₂ chromatography eluting with 10% ethylacetate in hexane to yield of pure intermediate (2.5 g, 61%): ¹ H NMR(CDCl₃) δ=3.33p (d, 2H, J=0.6 Hz), 3.78p (s, 2H), 7.1p (s, 1H).

Step 4

Preparation of6-chloro-5,6-dihydro-3-trifluoroacetyl-4H-thieno[2,3-b]thiopyran-4-one

The compound from Step 3 (1.03 g, 5.0 mmol) was dissolved intetrahydrofuran (50 mL) and cooled to -78° C. A solution of sodiumbistrimethylsilylamide (5.0 mL of a 1.0M tetrahydrofuran solution) wasadded and the reaction stirred for 0.75 hours at -78° C. Trifluoroacetylimidazole (0.68 mL, 6.0 mmol) was added and the reaction was warmed toroom temperature and stirred under a nitrogen atmosphere for 16 hours.At this time, 1N hydrochloric acid (300 mL) was added to the reactionfollowed by extraction with ether (350 mL). The organics were washedwith brine (200 mL), dried over MgSO₄ and concentrated in vacuo. Theresulting yellow oil was used without further purification.

Step 5

Preparation of4-[7-chloro-1,5-dihydro-3-trifluoromethyl-thieno[3',2':4,5]thiopyrano[3,2-c]pyrazol-1-yl]benzenesulfonamide

The compound from Step 4 (5.5 mmol) and 4-sulphonamidophenylhydrazinehydrochloride (1.47 g, 6.6 mmol) were dissolved in ethanol (100 mL) andheated to reflux for 16 hours. The reaction was concentrated in vacuoand the resulting solid dissolved in ethyl acetate (300 mL). Theorganics were washed with water (300 mL) followed by brine (200 mL) andwere then dried over MgSO₄ and concentrated in vacuo. The resulting oilwas chromatographed on silica gel eluting with a gradient of ethylacetate (from 20-40%) in hexane. This product was first crystallizedfrom ethyl acetate and isooctane, then from ethanol and water to yieldpure4-[7-chloro-1,5-dihydro-3-trifluoromethylthieno[3',2':4,5]thiopyrano[3,2-c]pyrazol-1-yl]benzenesulfonamide[0.35 g, 16% from Step 2]: mp 218°-220° C. (dec); ¹ H NMR (CDCl₃) δ=4.0p(s, 2H), 6.27p (s, 2H), 7.32p (s, 1H), 7.61(d, 2H, J=7.0 Hz), 8.02p (d,2H, J=7.0 Hz); ¹⁹ F NMR (acetone-d₆) δ=-59.25p (s, 3F). ##STR343##1-[4-(Aminosulfonyl)phenyl]-1,4-dihydro-[1]benzothiopyrano[4,3-c]-pyrazol-3-carbonitrile

Step 1

Preparation of1-[4-(aminosulfonyl)phenyl]-1,4-dihydro-[1]benzothiopyrano[4,3-c]pyrazol-3-carboxamide

The compound from Example 8 (11.31 g, 28.3 mmol) was placed in a 500 mLflask with methanol (200 mL), anhydrous ammonia was bubbled through thesolution, the flask was capped and allowed to stand. After 14 days thereaction was concentrated in vacuo and recrystallized from ethyl acetateto give the carboxamide as yellow solid (10.14 g, 93%): mp 238°-242° C.;¹ H NMR (acetone-d₆) 300 MHz 8.07 (d, J=8.7 Hz, 2H) 7.72 (d, J=8.7 Hz,2H) 7.49 (d, J=7.9 Hz, 1H) 7.30 (br s, 1H) 7.23 (dd, 1H) 7.02 (dd, 1H)6.91 (d, J=7.9 Hz, 1H) 6.80 (br s, 2H) 6.75 (br s, 1H) 4.28 (s, 2H).Mass spectrum: M+H=387.

Step 2

Preparation of1-[4-(aminosulfonyl)phenyl]-1,4-dihydro-[1]benzothiopyrano[4,3-c]pyrazol-3-carbonitrile

Dimethylformamide (10 mL) (DMF) was placed in a 250 mL flask and cooledto 0° C. Oxalyl chloride (2 mL, 23 mmol) was added and stirred for 15minutes. A solution of the product from Step 1 (3.34 g, 9 mmol) in DMF(13 mL) was added and the reaction was stirred for 0.8 hours, treatedwith pyridine (3.8 mL, 47 mmol), poured into 3N hydrochloric acid (30mL) and filtered to give a solid (2.86 g). The filtrate was extractedwith dichloromethane, washed with 3N hydrochloric acid and withsaturated NaHCO₃, dried over MgSO₄, concentrated in vacuo, combined withthe previously collected solid, purified by flash chromatography onsilica gel eluting with 1% methanol/dichloromethane, and recrystallizedfrom dichloromethane/isooctane to give a solid (2.44 g, mp 220°-222° C.)which was the DMF adduct of the desired product. The DMF adduct (2.44 g)was dissolved in dioxane (18 mL) and treated with a 4N solution ofhydrochloric acid in dioxane (10 mL). The solution was stirred at roomtemperature for 7.25 hours, heated to reflux for 42 hours, filtered, andconcentrated in vacuo. The residue was dissolved in methylene chloride,washed wtih water, dried over MgSO₄, and reconcentrated in vacuo to givea brown foam (2.43 g) which was a mixture of the desired product and itsadduct with DMF. The mixture was purified by flash chromatography onsilica gel eluting with 40% ethyl acetate/hexane to give the desiredproduct as a white solid (0.62 g, 19%): mp 211°-213° C.; ¹ H NMR(acetone-d₆) 300 MHz 8.10 (d, J=8.5 Hz, 2H) 7.76 (d, J=8.5 Hz, 2H) 7.54(d, J=7.7 Hz, 1H) 7.30 (dd, 1H) 7.07 (dd, 1H) 6.94 (d, J=8.1 Hz, 1H)6.82 (br s, 2H) 4.12 (s, 2H). High resolution mass Calc'd. for C₁₇ H₁₂N₄ O₂ S₂ : 368.0402. Found: 368.0368. ##STR344##4-[1,4-Dihydro-6-fluoro-7-methoxy-3-(trifluoromethyl)[1]benzopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide

Step 1

Preparation of 2-fluoro-3-methoxyphenyl)-3-oxo-propanoic acid

A solution of 2-fluoro-3-methoxybenzyl alcohol (1.57 g, 9.22 mmol),chloroacetic acid (1.72 g, 18.2 mmol), and ethanol (0.04 mL) in 20 mL ofanhydrous tetrahydrofuran was added to a mixture of sodium hydride (2.29g, 95.2 mmol) in 10 mL of anhydrous tetrahydrofuran dropwise over 10minutes at 0° C. The cooling bath was removed and the solution warmed toroom temperature and then was heated to reflux for 14 hours. Thesolution was cooled to room temperature, acidified with 3N hydrochloricacid, and extracted with ether. The ethereal phase was washed withbrine, dried over anhydrous MgSO₄, filtered, and concentrated in vacuoto provide a yellow solid (2.04 g, 100%) that was used directly in thenext step: ¹ H NMR (CDCl₃ /300 MHz) 8.60 (brs, 1H) , 7.08-6.93 (m, 3H),4.72 (d, J=1.4 Hz, 2H), 4.17 (s, 2H), 3.88 (s, 3H); ¹⁹ F NMR (CDCl₃ /282MHz) -141.50 (t). Mass spectrum M+Li=221.

Step 2

Preparation of 7-methoxy-8-fluoroisochroman-4-one

A solution of 2-fluoro-3-methoxyphenyl)-3-oxo-propanoic acid from Step 1(1.96 g, 8.6 mmol) in 4 mL of trifluoroacetic acid and 2 mL oftrifluoroacetic anhydride was stirred at room temperature for 1 hour.The solution was concentrated in vacuo, the residue dissolved in ether,and the ethereal solution was washed with saturated aqueous NaHCO₃,brine, dried over anhydrous MgSO₄, filtered and concentrated in vacuo togive a solid that was purified by flash chromatography to provide 0.37 g(32%) of the desired ketone. The aqueous phase from the NaHCO₃ wasacidified, extracted with ether, washed with brine, dried over anhydrousMgSO₄, filtered, and concentrated in vacuo to provide 1.13 g, ofrecovered 2-fluoro-3-methoxyphenyl)-3-oxo-propanoic acid: mp 112°-118°C.; ¹ H NMR (CDCl₃ /300 MHz) 7.86 (dd, J=8.66, 1.41 Hz, 1H), 7.00(apparent t, J=8.26 Hz, 1H), 4.96 (s, 2H), 4.31 (S, 2H), 3.97 (S, 3H);¹⁹ F NMR (CDCl₃ /282 MHz) -142.2 (d). Mass spectrum M⁺ =196.

Step 3

Preparation of 7-methoxy-8-fluoro-3-(trifluoroacetyl)isochroman-4-one

A solution of 7-methoxy-8-fluoroisochroman-4-one from Step 2 (370 mg,1.76 mmol) and ethyl trifluoroacetate (290 mg, 2.04 mmol) in 8 mL ofanhydrous tetrahydrofuran was treated with a solution of 25% sodiummethoxide in methanol (570 mg, 2.64 mmol). The solution was stirred atroom temperature for 16 hours, treated with excess 3N hydrochloric acid,and extracted with ether. The ethereal extract was washed with brine,dried over anhydrous MgSO₄, filtered and concentrated in vacuo to afford450 mg (88%) of pure7-methoxy-8-fluoro-3-(trifluoroacetyl)isochroman-4-one which was useddirectly in the next step without further purification.

Step 4

Preparation of4-[6-fluoro-1,4-dihydro-7-methoxy-3-(trifluoromethyl)-[1]benzopyrano[4,3-c]pyrazol-1-yl]benzonesulfonamide

7-Methoxy-8-fluoro-3-(trifluoroacetyl)isochroman-4-one from Step 3 (450mg, 1.47 mmol) and 4-sulfonamidophenylhydrazine hydrochloride (430 mg,1.92 mmol) were dissolved in 5 mL of anhydrous ethanol and heated toreflux for 45 minutes. The solution was concentrated in vacuo and theresidue was dissolved in ethyl acetate. The solution was washed with 3Nhydrochloric acid, brine, dried over anhydrous MgSO₄, filtered, andconcentrated in vacuo. The residue was crystallized from a mixture ofisooctane and ethyl acetate to afford4-[1,4-dihydro-6-fluoro-7-methoxy-3-(trifluoromethyl)-[1]benzopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamideas a white solid (200 mg, 30%): mp 289.5°-291.0° C.; ¹ H NMR (acetone d₆/300 MHz) 8.12 (d, J=8.4 Hz, 2H), 7.90 (d, J=8.5 Hz. 2H), 7.07 (dd,J=8.7, 8.5 Hz, 1H), 6.83 (br s, 2H), 6.75 (d, J=8.7 Hz, 1H), 5.45 (s,2H), 3.90 (s, 3H); ¹⁹ F NMR (acetone d₆ /282 MHz) -62.51 (s) , -140.97(d). High resolution mass spectrum Calc'd. for C₁₈ H₁₃ F₄ N₃ O₄ S:443.0563. Found: 443.0570.

The following compounds were obtained according to procedures similar tothat exemplified above and in the General Synthetic Schemes.

24)4-[7-chloro-1,5-dihydro-3-trifluoromethyl-thieno[3',2':4,5]thiopyrano-s-oxide[3,2-c]pyrazol-1-yl]benzenesulfonamide:mp=85° C. (dec).

25)4-[3-(difluoromethyl)-1,5-dihydro-6-fluoro-7-methoxy-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide:mp=256°-258° C.

26)4-[1,5-dihydro-7-fluoro-3-(trifluoromethyl)-[2]benzothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide:mp=240°-242° C.

27)[1-(4-aminosulfonylphenyl)-1,5-dihydro-7-fluoro-[2]benzothiopyrano[4,3-c]pyrazol-3-yl]carboxamide:mp=297°-298° C.

28)4-[1,5-dihydro-6-fluoro-7-methoxy-3-(trifluoromethyl)-[2]benzothiopyrano-S-oxide[4,3-c]pyrazol-1-yl]benzenesulfonamide:mp=>300° C.

29) methyl[1-(4-aminosulfonylphenyl)-1,5-dihydro-7-fluoro-[2]benzothiopyrano[4,3-c]pyrazol-3-yl]carboxylate:mp=241°-244° C.

30)4-[4,6-dihydro-7-fluoro-8-methoxy-3-(trifluoromethyl)-[2]benzothiepino[5,4-c]pyrazol-1-yl]benzenesulfonamide:mp=>133°-138° C.

BIOLOGICAL EVALUATION Rat Carrageenan Foot Pad Edema Test

The carrageenan foot edema test was performed with materials, reagentsand procedures essentially as described by Winter, et al., (Proc. Soc.Exp. Biol. Med., 111, 544 (1962)). Male Sprague-Dawley rats wereselected in each group so that the average body weight was as close aspossible. Rats were fasted with free access to water for over sixteenhours prior to the test. The rats were dosed orally (1 mL) withcompounds suspended in vehicle containing 0.5% methylcellulose and0.025% surfactant, or with vehicle alone. One hour later a subplantarinjection of 0.1 mL of 1% solution of carrageenan/sterile 0.9% salinewas administered and the volume of the injected foot was measured with adisplacement plethysmometer connected to a pressure transducer with adigital indicator. Three hours after the injection of the carrageenan,the volume of the foot was again measured. The average foot swelling ina group of drug-treated animals was compared with that of a group ofplacebo-treated animals and the percentage inhibition of edema wasdetermined (Otterness and Bliven, Laboratory Models for Testing NSAIDs,in Non-steroidal Anti-Inflammatory Drugs, (J. Lombardino, ed. 1985)).The % inhibition shows the % decrease from control paw volume determinedin this procedure and the data for selected compounds in this inventionare summarized in Table I.

Rat Carrageenan-induced Analgesia Test

The analgesia test using rat carrageenan was performed with materials,reagents and procedures essentially as described by Hargreaves, et al.,(Pain, 32, 77 (1988)). Male Sprague-Dawley rats were treated aspreviously described for the Carrageenan Foot Pad Edema test. Threehours after the injection of the carrageenan, the rats were placed in aspecial plexiglass container with a transparent floor having a highintensity lamp as a radiant heat source, positionable under the floor.After an initial twenty minute period, thermal stimulation was begun oneither the injected foot or on the contralateral uninjected foot. Aphotoelectric cell turned off the lamp and timer when light wasinterrupted by paw withdrawal. The time until the rat withdraws its footwas then measured. The withdrawal latency in seconds was determined forthe control and drug-treated groups, and percent inhibition of thehyperalgesic foot withdrawal determined. Results are shown in Table I.

                  TABLE I                                                         ______________________________________                                                   RAT PAW EDEMA  ANALGESIA                                           Example    % Inhibition.sup.1                                                                           % Inhibition.sup.1                                  ______________________________________                                        1          43             35                                                  2          28             29                                                  21         26             14                                                  ______________________________________                                         .sup.1 @ 30 mg/kg body weight                                            

Evaluation of COX I and COX II activity in vitro

The compounds of this invention exhibited inhibition in vitro of COX II.The COX II inhibition activity of the compounds of this inventionillustrated in the Examples was determined by the following methods.

a. Preparation of recombinant COX baculoviruses

A 2.0 kb fragment containing the coding region of either human or murineCOX-I or human or murine COX-II was cloned into a BamH1 site of thebaculovirus transfer vector pVL1393 (Invitrogen) to generate thebaculovirus transfer vectors for COX-I and COX-II in a manner similar tothe method of D. R. O'Reilly et al (Baculovirus Expression Vectors: ALaboratory Manual (1992)). Recombinant baculoviruses were isolated bytransfecting 4 μg of baculovirus transfer vector DNA into SF9 insectcells (2×10e8) along with 200 ng of linearized baculovirus plasmid DNAby the calcium phosphate method. See M. D. Summers and G. E. Smith, AManual of Methods for Baculovirus Vectors and Insect Cell CultureProcedures, Texas Agric. Exp. Station Bull. 1555 (1987). Recombinantviruses were purified by three rounds of plaque purification and hightiter (10E7-10E8 pfu/ml) stocks of virus were prepared. For large scaleproduction, SF9 insect cells were infected in 10 liter fermentors(0.5×10⁶ /ml) with the recombinant baculovirus stock such that themultiplicity of infection was 0.1. After 72 hours the cells werecentrifuged and the cell pellet homogenized in Tris/Sucrose (50 mM: 25%,pH 8.0) containing 1%3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). Thehomogenate was centrifuged at 10,000×G for 30 minutes, and the resultantsupernatant was stored at -80° C. before being assayed for COX activity.

b. Assay for COX I and COX II activity

COX activity was assayed as PGE₂ formed/μg protein/time using an ELISAto detect the prostaglandin released. CHAPS-solubilized insect cellmembranes containing the appropriate COX enzyme were incubated in apotassium phosphate buffer (50 mM, pH 8.0) containing epinephrine,phenol, and heme with the addition of arachidonic acid (10 μM).Compounds were pre-incubated with the enzyme for 10-20 minutes prior tothe addition of arachidonic acid. Any reaction between the arachidonicacid and the enzyme was stopped after ten minutes at 37° C./roomtemperature by transferring 40 μl of reaction mix into 160 μl ELISAbuffer and 25 μM indomethacin. The PGE₂ formed was measured by standardELISA technology (Cayman Chemical). Results are shown in Table II.

                  TABLE II                                                        ______________________________________                                                    Human COX II                                                                              Human COX I                                           Example     (D.sub.50 μM                                                                           ID.sub.50 μM                                       ______________________________________                                        1           <.1         2.7                                                   2           <.1         >100                                                  3           1.3         7.1                                                   4           .5                                                                5           4.8         24.4                                                  6           23.5        11.1                                                  7           .5          9.7                                                   8           .5                                                                9           48.2        >100                                                  10          <.1         6.2                                                   11          52          >100                                                  12          95          >100                                                  13          <.1         <.1                                                   14          .2          4.6                                                   15          <.1         .3                                                    16          <.1         .4                                                    17          <.1         .8                                                    18          <.1         3.7                                                   19          <.1         .30                                                   20          <.1         <.1                                                   21          <.1         8.7                                                   22          3.5         51                                                    24          45.6        91.1                                                  25          <.1         >100                                                  26          <.1         .3                                                    27          4.7         >100                                                  28          1.2         >100                                                  29          .8          13.2                                                  30          2.2         73.4                                                  ______________________________________                                    

Also embraced within this invention is a class of pharmaceuticalcompositions comprising one or more compounds of Formula I inassociation with one or more non-toxic, pharmaceutically-acceptablecarriers and/or diluents and/or adjuvants (collectively referred toherein as "carrier" materials) and, if desired, other activeingredients. The compounds of the present invention may be administeredby any suitable route, preferably in the form of a pharmaceuticalcomposition adapted to such a route, and in a dose effective for thetreatment intended. The compounds and composition may, for example, beadministered intravascularly, intraperitoneally, subcutaneously,intramuscularly or topically.

For oral administration, the pharmaceutical composition may be in theform of, for example, a tablet, capsule, suspension or liquid. Thepharmaceutical composition is preferably made in the form of a dosageunit containing a particular amount of the active ingredient. Examplesof such dosage units are tablets or capsules. The active ingredient mayalso be administered by injection as a composition wherein, for example,saline, dextrose or water may be used as a suitable carrier.

The amount of therapeutically active compound that is administered andthe dosage regimen for treating a disease condition with the compoundsand/or compositions of this invention depends on a variety of factors,including the age, weight, sex and medical condition of the subject, theseverity of the disease, the route and frequency of administration, andthe particular compound employed, and thus may vary widely. Thepharmaceutical compositions may contain active ingredient in the rangeof about 0.1 to 2000 mg, preferably in the range of about 0.5 to 500 mgand most preferably between about 1 and 100 mg. A daily dose of about0.01 to 100 mg/kg body weight, preferably between about 0.1 and about 50mg/kg body weight and most preferably between about 1 to 20 mg/kg bodyweight, may be appropriate. The daily dose can be administered in one tofour doses per day.

For therapeutic purposes, the compounds of this invention are ordinarilycombined with one or more adjuvants appropriate to the indicated routeof administration. If administered per os, the compounds may be admixedwith lactose, sucrose, starch powder, cellulose esters of alkanoicacids, cellulose alkyl esters, talc, stearic acid, magnesium stearate,magnesium oxide, sodium and calcium salts of phosphoric and sulfuricacids, gelatin, acacia gum, sodium alginate, polyvinylpyrrolidone,and/or polyvinyl alcohol, and then tableted or encapsulated forconvenient administration. Such capsules or tablets may contain acontrolled-release formulation as may be provided in a dispersion ofactive compound in hydroxypropylmethyl cellulose. Formulations forparenteral administration may be in the form of aqueous or non-aqueousisotonic sterile injection solutions or suspensions. These solutions andsuspensions may be prepared from sterile powders or granules having oneor more of the carriers or diluents mentioned for use in theformulations for oral administration. The compounds may be dissolved inwater, polyethylene glycol, propylene glycol, ethanol, corn oil,cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride,and/or various buffers. Other adjuvants and modes of administration arewell and widely known in the pharmaceutical art.

Although this invention has been described with respect to specificembodiments, the details of these embodiments are not to be construed aslimitations.

What is claimed is:
 1. A compound of Formula I ##STR345## wherein A is--(CH₂)_(m) --X--(CH₂)_(n) --; wherein X is selected from S(O)_(p), andO;wherein m is 0 to 3, inclusive; wherein n is 0 to 3, inclusive;wherein p is 0 to 2, inclusive; wherein B is heteroaryl; wherein R¹ isselected from hydrido, halo, haloalkyl, cyano, nitro, formyl,alkoxycarbonyl, carboxyl, carboxyalkyl, alkoxycarbonylalkyl, amidino,cyanoamidino, aminocarbonyl, alkoxy, alkoxyalkyl, aminocarbonylalkyl,N-alkylaminocarbonyl, N-arylaminocarbonyl, N,N-dialkylaminocarbonyl,N-alkyl-N-arylaminocarbonyl, alkylcarbonyl, alkylcarbonylalkyl,hydroxyalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl,alkylsulfinylalkyl, alkylsulfonylalkyl, N-alkylsulfamyl, N-arylsulfamyl,arylsulfonyl, N, N-dialkylsulfamyl, N-alkyl-N-arylsulfamyl andheterocyclic; wherein R² is selected from aryl and heteroaryl, whereinR² is optionally substituted at a substitutable position with one ormore radicals selected from alkylsulfonyl, sulfamyl, halo, alkyl,alkoxy, hydroxyl and haloalkyl; and wherein R⁴ is one or more radicalsselected from hydrido, halo, alkylthio, alkylsulfinyl, alkyl,alkylsulfonyl, cyano, carboxyl, alkoxycarbonyl, amido,N-alkylaminocarbonyl, N-arylaminocarbonyl, N,N-dialkylaminocarbonyl,N-alkyl-N-arylaminocarbonyl, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl,haloalkoxy, sulfamyl, N-alkylsulfamyl, amino, N-alkylamino,N,N-dialkylamino, heterocyclic, nitro and acylamino; provided either R⁴is sulfamyl or alkylsulfonyl, or R² is substituted with sulfamyl oralkylsulfonyl; or a pharmaceutically-acceptable salt thereof. 2.Compound of claim 1 wherein A is --(CH₂)_(m) --X--(CH₂)_(n) --;wherein Xis selected from S(O)_(p), and O; wherein m is 0 to 3, inclusive;wherein n is 0 to 3, inclusive; wherein p is 0 to 2, inclusive; whereinB is selected from five and six membered heteroaryl; wherein R¹ isselected from halo, lower haloalkyl, cyano, nitro, formyl, loweralkoxycarbonyl, lower carboxyalkyl, lower alkoxycarbonylalkyl, amidino,cyanoamidino, lower alkoxy, lower alkoxyalkyl, aminocarbonyl, loweraminocarbonylalkyl, lower N-alkylaminocarbonyl, N-phenylaminocarbonyl,lower N,N-dialkylaminocarbonyl, lower N-alkyl-N-phenylaminocarbonyl,lower alkylcarbonyl, lower alkylcarbonylalkyl, lower hydroxyalkyl, loweralkylthio, lower alkylsulfinyl, lower alkylsulfonyl, loweralkylthioalkyl, lower alkylsulfinylalkyl, lower alkylsulfonylalkyl,lower N-alkylsulfamyl, N-phenylsulfamyl, phenylsulfonyl, lowerN,N-dialkylsulfamyl, lower N-alkyl-N-phenylsulfamyl and five-sevenmembered heterocyclic; wherein R² is selected from phenyl and five orsix membered heteroaryl, wherein R² is optionally substituted at asubstitutable position with one or more radicals selected from loweralkylsulfonyl, sulfamyl, halo, lower alkyl, lower alkoxy, hydroxyl andlower haloalkyl; and wherein R⁴ is one or more radicals selected fromhydrido, halo, lower alkylthio, lower alkylsulfinyl, lower alkyl, loweralkylsulfonyl, cyano, carboxyl, lower alkoxycarbonyl, aminocarbonyl,lower N-alkylaminocarbonyl, N-phenylaminocarbonyl, lowerN,N-dialkylaminocarbonyl, lower N-alkyl-N-phenylaminocarbonyl, lowerhaloalkyl, hydroxyl, lower alkoxy, lower hydroxyalkyl, lower haloalkoxy,sulfamyl, lower N-alkylsulfamyl, amino, lower N-alkylamino, lowerN,N-dialkylamino, five-seven membered heterocyclic, nitro and acylamino;or a pharmaceutically-acceptable salt thereof.
 3. Compound of claim 2wherein A is --(CH₂)_(m) --X--(CH₂)_(n) --; wherein X is S(O)_(p) or O;wherein m is 0, 1 or 2; wherein n is 0, 1 or 2; wherein p is 0, 1 or 2;wherein B is selected from five and six membered heteroaryl; wherein R¹is selected from halo, lower haloalkyl, cyano, formyl, loweralkoxycarbonyl, aminocarbonyl, lower alkoxycarbonylalkyl, lower alkoxy,lower alkoxyalkyl, lower aminocarbonylalkyl, lower N-alkylaminocarbonyl,N-phenylaminocarbonyl, lower N,N-dialkylaminocarbonyl, lowerN-alkyl-N-phenylaminocarbonyl and lower hydroxyalkyl; wherein R² isphenyl substituted at a substitutable position with a radical selectedfrom lower alkylsulfonyl and sulfamyl; and wherein R⁴ is one or moreradicals selected from hydrido, halo, lower alkylthio, loweralkylsulfinyl, lower alkyl, lower alkylsulfonyl, cyano, carboxyl, loweralkoxycarbonyl, aminocarbonyl, lower N-alkylaminocarbonyl, lowerN,N-dialkylaminocarbonyl, lower N-alkyl-N-phenylaminocarbonyl, lowerhaloalkyl, hydroxyl, lower alkoxy, lower hydroxyalkyl, amino, lowerN-alkylamino, lower N,N-dialkylamino, lower haloalkoxy and nitro; or apharmaceutically-acceptable salt thereof.
 4. Compound of claim 3 whereinA is --(CH₂)_(m) --X--(CH₂)_(n) --; wherein X is S(O)_(p) or O; whereinm is 0 or 1; wherein n is 0 or 1; wherein p is 0 or 1; wherein B isselected from five and six membered heteroaryl; wherein R¹ is selectedfrom lower haloalkyl, cyano, formyl, lower alkoxycarbonyl, lower alkoxy,lower N-alkylaminocarbonyl, N-phenylaminocarbonyl, lowerN,N-dialkylaminocarbonyl and lower N-alkyl-N-phenylaminocarbonyl;wherein R² is phenyl substituted at a substitutable position with aradical selected from lower alkylsulfonyl and sulfamyl; and wherein R⁴is one or more radicals selected from hydrido, halo, lower alkylthio,lower alkylsulfinyl, lower alkyl, cyano, carboxyl, lower alkoxycarbonyl,aminocarbonyl, lower haloalkyl, hydroxyl, lower alkoxy, amino, lowerN-alkylamino, lower N,N-dialkylamino, lower hydroxyalkyl and lowerhaloalkoxy; or a pharmaceutically-acceptable salt thereof.
 5. Compoundof claim 4 wherein A is --(CH₂)_(m) --X--(CH₂)_(n) --; wherein X isS(O)_(p) or O; wherein m is 0 or 1; wherein n is 0 or 1; wherein p is 0or 1; wherein B is selected from thienyl, pyridyl, furyl, oxazolyl,thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, triazolyl,pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, thiaimidazolyl,oxoimidazolyl, azaoxazolyl, azathiazolyl and pyrrolyl;wherein R¹ isselected from fluoromethyl, difluoromethyl, trifluoromethyl,chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl,heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl,difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, cyano,formyl, carboxyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl,tert-butoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl,pentoxycarbonyl, aminocarbonyl, methoxy, ethoxy, propoxy, n-butoxy,N-methylaminocarbonyl, N-phenylaminocarbonyl, N,N-dimethylaminocarbonyl,N-methyl-N-phenylaminocarbonyl and methylcarbonyl; wherein R² is phenylsubstituted at a substitutable position with a radical selected frommethylsulfonyl and sulfamyl; wherein R⁴ is optionally substituted withone or more radicals selected from hydrido, fluoro, chloro, bromo,methylthio, ethylthio, isopropylthio, tert-butylthio, isobutylthio,hexylthio, methylsulfinyl, ethylsulfinyl, isopropylsulfinyl,tert-butylsulfinyl, isobutylsulfinyl, hexylsulfinyl, methyl, ethyl,isopropyl, tert-butyl, isobutyl, hexyl, cyano, carboxyl,methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl,tert-butoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl,pentoxycarbonyl, aminocarbonyl, fluoromethyl, difluoromethyl,trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl,pentafluoroethyl, heptafluoropropyl, difluorochloromethyl,dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl,dichloropropyl, hydroxyl, methoxy, methylenedioxy, ethoxy, propoxy,n-butoxy, hydroxymethyl and trifluoromethoxy; or apharmaceutically-acceptable salt thereof.
 6. Compound of claim 5 whichis4-[7-chloro-1,5-dihydro-3-trifluoromethyl-[2]thienothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide,or a pharmaceutically-acceptable salt thereof.
 7. A compound of FormulaII ##STR346## wherein A is --(CH₂)_(m) --X--(CH₂)_(n) --; wherein X isS(O)_(p) or O;wherein m is 0 or 1; wherein n is 0 or 1; wherein p is 0or 1; wherein B is heteroaryl; wherein R¹ is selected from haloalkyl,aminocarbonyl, alkoxycarbonyl and cyano; wherein R⁴ is one or moreradicals selected from hydrido, halo, alkyl and alkoxy; and wherein R⁵is selected from alkyl and amino; or a pharmaceutically-acceptable saltthereof.
 8. Compound of claim 7 wherein A is --(CH₂)_(m) --X--(CH₂)_(n)--; wherein X is S(O)_(p) or O; wherein m is 0 or 1; wherein n is 0 or1; wherein p is 0 or 1; wherein B is five membered heteroaryl; whereinR¹ is selected from lower haloalkyl, aminocarbonyl, lower alkoxycarbonyland cyano; wherein R⁴ is one or more radicals selected from hydrido,halo, lower alkyl and lower alkoxy; and wherein R⁵ is selected fromlower alkyl and amino; or a pharmaceutically-acceptable salt thereof. 9.Compound of claim 8 wherein A is --(CH₂)_(m) --X--(CH₂)_(n) --; whereinX is S(O)_(p) or O; wherein m is 0 or 1; wherein n is 0 or 1; wherein pis 0 or 1; wherein B is selected from thienyl, furyl and pyrrolyl;wherein R¹ is selected from fluoromethyl, difluoromethyl,trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl,pentafluoroethyl, heptafluoropropyl, difluorochloromethyl,dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl,dichloropropyl, aminocarbonyl, methoxycarbonyl, ethoxycarbonyl,propoxycarbonyl, butoxycarbonyl and cyano; wherein R⁴ is one or moreradicals selected from hydrido, fluoro, chloro, bromo, methyl, ethyl,isopropyl, tert-butyl, isobutyl, hexyl, methoxy, methylenedioxy, ethoxy,propoxy, n-butoxy and tert-butoxy; and wherein R⁵ is selected frommethyl and amino; or a pharmaceutically-acceptable salt thereof. 10.Compound of claim 5 selected from compounds, and their pharmaceuticallyacceptable salts, of the group consistingof4-[7-chloro-1,5-dihydro-3-trifluoromethyl-[2]thienothiopyrano[4,3-c]pyrazol-1-yl]benzenesulfonamide;4-[7-chloro-1,5-dihydro-3-trifluoromethylthieno[3',2':4,5]thiopyrano[3,2-c]pyrazol-1-yl]benzenesulfonamide;4-[7- chloro-1,5- dihydro-3-trifluoromethylthieno[3',2':4,5]thiopyrano-S-oxide[3,2-c]pyrazol-1-yl]benzenesulfonamide;4-[1,5-dihydro-3-(trifluoromethyl)furano[2',3':4,5]thiopyrano [3,2-c]pyrazol-1-yl]benzenesulfonamide;4-[1,5-dihydro-3-(trifluoromethyl)oxazolo[4',5':4,5]thiopyrano[3,2-c]pyrazol-1-yl]benzenesulfonamide;4-[1,5-dihydro-3-(trifluoromethyl)thiazolo[5',4':4,5]thiopyrano[3,2-c]pyrazol-1-yl]benzenesulfonamide;1,5-dihydro-1-(4-methoxyphenyl)-3-(trifluoromethyl)thieno[3',2':4,5]thiopyrano[3,2-c]pyrazole-7-sulfonamide; and4-[1,5-dihydro-3-(trifluoromethyl)pyrazolo[3',4':5,6]thiopyrano[3,4-b]pyridin-1-yl]benzenesulfonamide.
 11. A pharmaceutical compositioncomprising a therapeutically-effective amount of a compound, saidcompound selected from a family of compounds of claim 1; or apharmaceutically-acceptable salt thereof.
 12. A pharmaceuticalcomposition comprising a therapeutically-effective amount of a compound,said compound selected from a family of compounds of claim 2; or apharmaceutically-acceptable salt thereof.
 13. A pharmaceuticalcomposition comprising a therapeutically-effective amount of a compound,said compound selected from a family of compounds of claim 3; or apharmaceutically-acceptable salt thereof.
 14. A pharmaceuticalcomposition comprising a therapeutically-effective amount of a compound,said compound selected from a family of compounds of claim 4; or apharmaceutically-acceptable salt thereof.
 15. A pharmaceuticalcomposition comprising a therapeutically-effective amount of a compound,said compound selected from a family of compounds of claim 5; or apharmaceutically-acceptable salt thereof.
 16. A pharmaceuticalcomposition comprising a therapeutically-effective amount of a compound,said compound selected from a family of compounds of claim 10; or apharmaceutically-acceptable salt thereof.
 17. A pharmaceuticalcomposition comprising a therapeutically-effective amount of a compound,said compound selected from a family of compounds of claim 6; or apharmaceutically-acceptable salt thereof.
 18. A method of treatinginflammation or an inflammation-associated disorder in a subject, saidmethod comprising administering to the subject having or susceptible tosaid inflammation or inflammation-associated disorder, atherapeutically-effective amount of a compound of claim 1; or apharmaceutically-acceptable salt thereof.
 19. A method of treatinginflammation or an inflammation-associated disorder in a subject, saidmethod comprising administering to the subject having or susceptible tosaid inflammation or inflammation-associated disorder, atherapeutically-effective amount of a compound of claim 2; or apharmaceutically-acceptable salt thereof.
 20. A method of treatinginflammation or an inflammation-associated disorder in a subject, saidmethod comprising administering to the subject having or susceptible tosaid inflammation or inflammation-associated disorder, atherapeutically-effective amount of a compound of claim 3; or apharmaceutically-acceptable salt thereof.
 21. A method of treatinginflammation or an inflammation-associated disorder in a subject, saidmethod comprising administering to the subject having or susceptible tosaid inflammation or inflammation-associated disorder, atherapeutically-effective amount of a compound of claim 4; or apharmaceutically-acceptable salt thereof.
 22. A method of treatinginflammation or an inflammation-associated disorder in a subject, saidmethod comprising administering to the subject having or susceptible tosaid inflammation or inflammation-associated disorder, atherapeutically-effective amount of a compound of claim 5; or apharmaceutically-acceptable salt thereof.
 23. A method of treatinginflammation or an inflammation-associated disorder in a subject, saidmethod comprising administering to the subject having or susceptible tosaid inflammation or inflammation-associated disorder, atherapeutically-effective amount of a compound of claim 10; or apharmaceutically-acceptable salt thereof.
 24. A method of treatinginflammation or an inflammation-associated disorder in a subject, saidmethod comprising administering to the subject having or susceptible tosaid inflammation or inflammation-associated disorder, atherapeutically-effective amount of a compound of claim 6; or apharmaceutically-acceptable salt thereof.
 25. The method of claim 18 foruse in treatment of inflammation.
 26. The method of claim 18 for use intreatment of an inflammation-associated disorder.
 27. The method ofclaim 26 wherein the inflammation-associated disorder is arthritis. 28.The method of claim 26 wherein the inflammation-associated disorder ispain.
 29. The method of claim 26 wherein the inflammation-associateddisorder is fever.